Dietary Phenolic Acids and Flavonoids as Potential Anti-Cancer Agents: Current State of the Art and Future Perspectives

Author(s): Ramesh K. Bonta*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 20 , Issue 1 , 2020

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Graphical Abstract:


Background: Cancer is a rapidly growing disease and the second most leading cause of death worldwide. Breast, colon, lung, and prostate cancer are the most diagnosed types of cancer among the majority of the population. The prevalence of these cancers is increasing rapidly due to the lack of effective drugs. The search for anti-cancer bioactive components from natural plant sources is gaining immense significance. The aim of the paper is to introduce the readers about the in vitro and in vivo biochemical mechanisms of phenolic acids and flavonoids in these four types of cancers.

Methods: A literature search was carried out in databases, including Scopus, SciFinder, Springer, Science direct and Google. The main keywords used were fruits & vegetables, phenolic acids, flavonoids, anticancer, bioavailability, etc. The data obtained were integrated and analyzed.

Results: The study revealed the potential molecular mechanisms of phenolic acids and flavonoids, which include the induction of apoptosis, inhibition of cell proliferation, cell-cycle arrest, induction of Poly ADP ribose polymerase cleavage, downregulation of Matrix metalloproteinases-2 and Matrix metalloproteinases-9 activities, decreased levels of B-cell lymphoma-2, etc. Promising effects of phenolic acids and flavonoids have been observed against breast, colon, lung and prostate cancers.

Conclusion: The in vitro and in vivo anti-cancer mechanisms of phenolic acids and flavonoids have been revealed in this study. With the knowledge of specific molecular targets and the structural-functional relationship of bioactive compounds, the current review will open a new gateway for the scientific community and provide them a viable option to exploit more of these compounds for the development of novel and efficacious anticancer compounds.

Keywords: Fruits, vegetables, phenolic acids, flavonoids, bioavailability, anti-cancer.

Jabir, N.R.; Firoz, C.K.; Bhushan, A.; Tabrez, S.; Kamal, M.A. The use of azoles containing natural products in cancer prevention and treatment: An overview. Anticancer. Agents Med. Chem., 2018, 18(1), 6-14.
[] [PMID: 27198985]
Wu-Wang, H.; Yi-Zhong, C.; Zhang, Y. Natural phenolic compounds from medicinal herbs and dietary plants. Potential use for cancer prevention. Nutr. Cancer, 2009, 62(1), 1-20.
[] [PMID: 19116871]
Javadi, B. Diet therapy for cancer prevention and treatment based on traditional Persian medicine. Nutr. Cancer, 2018, 70(3), 376-403.
[] [PMID: 29543522]
World Health Organization (WHO). Cancer, Geneva, Switzerland. February 20, 2017)..
Hussain, S.A.; Sulaiman, A.A.; Balch, C.; Chauhan, H.; Alhadidi, Q.M.; Tiwari, A.K. Natural polyphenols in cancer chemoresistance. Nutr. Cancer, 2016, 68(6), 879-891.
[] [PMID: 27366999]
Mateen, S.; Raina, K.; Agarwal, R. Chemopreventive and anti-cancer efficacy of silibinin against growth and progression of lung cancer. Nutr. Cancer, 2013, 65(01)(Suppl. 1), 3-11.
[] [PMID: 23682778]
Neuhouser, M.L. Dietary flavonoids and cancer risk: evidence from human population studies. Nutr. Cancer, 2004, 50(1), 1-7.
[] [PMID: 15572291]
Kumar, B.R.; Anupam, A.; Manchikanti, P.; Rameshbabu, A.P.; Dasgupta, S.; Dhara, S. Identification and characterization of bioactive phenolic constituents, anti-proliferative, and anti-angiogenic activity of stem extracts of Basella alba and rubra. J. Food Sci. Technol., 2018, 55(5), 1675-1684.
[] [PMID: 29666520]
Kaur, V.; Kumar, M.; Kumar, A.; Kaur, K.; Dhillon, V.S.; Kaur, S. Pharmacotherapeutic potential of phytochemicals: Implications in cancer chemoprevention and future perspectives. Biomed. Pharmacother., 2018, 97, 564-586.
[] [PMID: 29101800]
Conlon, L.E.; Erdman, J.W., Jr Nonnutritive Components in Foods and Cancer Risk. In: Preventive Nutrition, Nutrition and Health;; Bendich and Deckelbaum, Ed.; Springer International Publishing:Switzerland. , 2015; 5, pp. 215-242.
Aggarwal, B.B.; Shishodia, S. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem. Pharmacol., 2006, 71(10), 1397-1421.
[] [PMID: 16563357]
Shanmugam, M.K.; Lee, J.H.; Chai, E.Z.; Kanchi, M.M.; Kar, S.; Arfuso, F.; Dharmarajan, A.; Kumar, A.P.; Ramar, P.S.; Looi, C.Y.; Mustafa, M.R.; Tergaonkar, V.; Bishayee, A.; Ahn, K.S.; Sethi, G. Cancer prevention and therapy through the modulation of transcription factors by bioactive natural compounds. Semin. Cancer Biol., 2016, 40-41, 35-47.
[] [PMID: 27038646]
Kumar, B.R. Application of HPLC and ESI-MS techniques in the analysis of phenolic acids and flavonoids from green leafy vegetables (GLVs). J. Pharm. Anal., 2017, 7(6), 349-364.
[] [PMID: 29404060]
Singh, S.; Sharma, B.; Kanwar, S.S.; Kumar, A. Lead phytochemicals for anticancer drug development. Front. Plant Sci., 2016, 7, 1667.
[] [PMID: 27877185]
González-Vallinas, M.; González-Castejón, M.; Rodríguez-Casado, A.; Ramírez de Molina, A. Dietary phytochemicals in cancer prevention and therapy: a complementary approach with promising perspectives. Nutr. Rev., 2013, 71(9), 585-599.
[] [PMID: 24032363]
Lope, V.; Martín, M.; Castelló, A.; Casla, S.; Ruiz, A.; Baena-Cañada, J.M.; Casas, A.M.; Calvo, L.; Bermejo, B.; Muñoz, M.; Ramos, M.; de Juan-Ferré, A.; Jara, C.; Antón, A.; Jimeno, M.Á.; Lluch, A.; Antolín, S.; García-Sáenz, J.Á.; Estévez, P.; Arriola-Arellano, E.; Gavilá, J.; Pérez-Gómez, B.; Carrasco, E.; Pollán, M. Physical activity and breast cancer risk by pathological subtype. Gynecol. Oncol., 2017, 144(3), 577-585.
[] [PMID: 28057355]
Adebamowo, C.A.; Hu, F.B.; Cho, E.; Spiegelman, D.; Holmes, M.D.; Willett, W.C. Dietary patterns and the risk of breast cancer. Ann. Epidemiol., 2005, 15(10), 789-795.
[] [PMID: 16257363]
Key, T.J. Fruit and vegetables and cancer risk. Br. J. Cancer, 2011, 104(1), 6-11.
[] [PMID: 21119663]
Emaus, M.J.; Peeters, P.H.M.; Bakker, M.F.; Overvad, K.; Tjønneland, A.; Olsen, A.; Romieu, I.; Ferrari, P.; Dossus, L.; Boutron-Ruault, M.C.; Baglietto, L.; Fortner, R.T.; Kaaks, R.; Boeing, H.; Trichopoulou, A.; Lagiou, P.; Trichopoulos, D.; Masala, G.; Pala, V.; Panico, S.; Tumino, R.; Polidoro, S.; Skeie, G.; Lund, E.; Weiderpass, E.; Quirós, J.R.; Travier, N.; Sánchez, M.J.; Chirlaque, M.D.; Ardanaz, E.; Dorronsoro, M.; Winkvist, A.; Wennberg, M.; Bueno-de-Mesquita, H.B.; Khaw, K.T.; Travis, R.C.; Key, T.J.; Aune, D.; Gunter, M.; Riboli, E.; van Gils, C.H. Vegetable and fruit consumption and the risk of hormone receptor-defined breast cancer in the EPIC cohort. Am. J. Clin. Nutr., 2016, 103(1), 168-177.
[] [PMID: 26607934]
Losurdo, G.; Principi, M.; Girardi, B.; Pricci, M.; Barone, M.; Ierardi, E.; Di Leo, A. Histamine and histaminergic receptors in colorectal cancer: From Basic Science to evidence-based medicine. Anticancer. Agents Med. Chem., 2018, 18(1), 15-20.
[] [PMID: 26996193]
Araújo, J.R.; Gonçalves, P.; Martel, F. Chemopreventive effect of dietary polyphenols in colorectal cancer cell lines. Nutr. Res., 2011, 31(2), 77-87.
[] [PMID: 21419311]
Schatzkin, A. Dietary change as a strategy for preventing cancer. Cancer Metastasis Rev., 1997, 16(3-4), 377-392.
[] [PMID: 9433646]
van Breda, S.G.J.; de Kok, T.M.C.M.; van Delft, J.H.M. Mechanisms of colorectal and lung cancer prevention by vegetables: A genomic approach. J. Nutr. Biochem., 2008, 19(3), 139-157.
[] [PMID: 17651960]
Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 2015, 136(5), E359-E386.
[] [PMID: 25220842]
Meng, H.; Hu, W.; Chen, Z.; Shen, Y. Fruit and vegetable intake and prostate cancer risk: A meta-analysis. Asia Pac. J. Clin. Oncol., 2014, 10(2), 133-140.
[] [PMID: 23551391]
Greenwald, P. Diet and cancer prevention in the United States. Food Factors for Cancer Prevention; H. Ohigashi, T, Osawa, J, Terao; Watanabe, S; Yoshikawa, T., Ed.; Springer: Japan, 1997, Vol. 1, pp. 30-35.
Pennington, J.A.T.; Fisher, R.A. Classification of fruits and vegetables. J. Food Compos. Anal., 2009, 22S, S23-S31.
Hervert-Hernandez, D.; Garcia, O.P.; Rosado, J.L.; Goni, I. The contribution of fruits and vegetables to dietary intake of polyphenols and antioxidant capacity in a Mexican rural diet: Importance of fruit and vegetable variety. Food Res. Int., 2011, 44(5), 1182-1189.
Soerjomataram, I.; Oomen, D.; Lemmens, V.; Oenema, A.; Benetou, V.; Trichopoulou, A.; Coebergh, J.W.; Barendregt, J.; de Vries, E. Increased consumption of fruit and vegetables and future cancer incidence in selected European countries. Eur. J. Cancer, 2010, 46(14), 2563-2580.
[] [PMID: 20843486]
Li, Y.; Li, C.; Sun, Y.; Niu, Y.; Liu, L.; Mei, Q. Are the ingredients extracted from fruits and vegetables superior to fruits and vegetables in cancer prevention? Med. Hypotheses, 2010, 75(1), 77-78.
[] [PMID: 20189315]
Liaudanskas, M.; Viskelis, P.; Kviklys, D.; Raudonis, R.; Janulis, V. A comparative study of phenolic content in apple fruits. Int. J. Food Prop., 2015, 18(5), 945-953.
Passo Tsamo, C.V.; Herent, M.F.; Tomekpe, K.; Happi Emaga, T.; Quetin-Leclercq, J.; Rogez, H.; Larondelle, Y.; Andre, C. Phenolic profiling in the pulp and peel of nine plantain cultivars (Musa sp.). Food Chem., 2015, 167, 197-204.
[] [PMID: 25148979]
Mertz, C.; Cheynier, V.; Günata, Z.; Brat, P. Analysis of phenolic compounds in two blackberry species (Rubus glaucus and Rubus adenotrichus) by high-performance liquid chromatography with diode array detection and electrospray ion trap mass spectrometry. J. Agric. Food Chem., 2007, 55(21), 8616-8624.
[] [PMID: 17896814]
Chiari-Andreo, B.G.; Trovatti, E.; Marto, J.; Jose de Almeida-Cincotto, M.G.; Melero, A.; Correa, M.A.; Chiavacci, L.A.; Riberio, H.; Garrigues, T.; Borges Issac, V.L. Guava: Phytochemical composition of a potential source of antioxidants for cosmetic and/or dermatological applications. Braz. J. Pharm. Sci., 2017, 53(2), 1-10.
Nicoletti, I.; Bello, C.; De Rossi, A.; Corradini, D. Identification and quantification of phenolic compounds in grapes by HPLC-PDA-ESI-MS on a semimicro separation scale. J. Agric. Food Chem., 2008, 56(19), 8801-8808.
[] [PMID: 18781764]
Ayyanar, M.; Subash-Babu, P. Syzygium cumini (L.) Skeels: A review of its phytochemical constituents and traditional uses. Asian Pac. J. Trop. Biomed., 2012, 2(3), 240-246.
[] [PMID: 23569906]
Al-Shwyeh, H.A.; Mohammed, A.S.; Abdullah, R. Identification and quantification of phenolic compounds in Mangifera indica Waterlily Kernel and their free radical scavenging activity. JOAAT, 2015, 2(1), 1-7.
Agcam, E.; Akyıldız, A.; Akdemir Evrendilek, G. Comparison of phenolic compounds of orange juice processed by pulsed electric fields (PEF) and conventional thermal pasteurisation. Food Chem., 2014, 143, 354-361.
[] [PMID: 24054251]
Zunjar, V.; Mammen, D.; Trivedi, B.M. Antioxidant activities and phenolics profiling of different parts of Carica papaya by LCMS-MS. Nat. Prod. Res., 2015, 29(22), 2097-2099.
[] [PMID: 25495879]
Yapo, E.S.; Kouakou, H.T.; Kouakou, L.K.; Kouadio, J.Y.; Kouame, P.; Merillon, J.M. Phenolic profiles of pineapple fruits (Ananas comosus L. Merrill). Influence of the origin of suckers. Aust. J. Basic Appl. Sci., 2011, 5(6), 1372-1378.
Barathikannan, K.; Venkatadri, B.; Khusro, A.; Al-Dhabi, N.A.; Agastian, P.; Arasu, M.V.; Choi, H.S.; Kim, Y.O. Chemical analysis of Punica granatum fruit peel and its in vitro and in vivo biological properties. BMC Complement. Altern. Med., 2016, 16, 264.
[] [PMID: 27476116]
Kujala, T.S.; Vienola, M.S.; Klika, K.D.; Loponen, J.M.; Pihlaja, K. Betalain and phenolic compositions of four beetroot (Beta vulgaris) cultivars. Eur. Food Res. Technol., 2002, 214(6), 505-510.
Singh, J.P.; Kaur, A.; Shevkani, K.; Singh, N. Composition, bioactive compounds and antioxidant activity of common Indian fruits and vegetables. J. Food Sci. Technol., 2016, 53(11), 4056-4066.
[] [PMID: 28035161]
Jaiswal, R.; Kuhnert, N. Identification and characterization of the phenolic glycosides of Lagenaria siceraria Stand. (Bottle gourd) fruit by liquid chromatography-tandem mass spectrometry. J. Agric. Food Chem., 2014, 62(6), 1261-1271.
[] [PMID: 24447091]
Plumb, G.W.; Price, K.R.; Rhodes, M.J.; Williamson, G. Antioxidant properties of the major polyphenolic compounds in broccoli. Free Radic. Res., 1997, 27(4), 429-435.
[] [PMID: 9416471]
dos Reis, L.C.R.; de Oliveira, V.R.; Hagen, M.E.K.; Jablonski, A.; Flores, S.H.; de Oliviera Rios, A. Carotenoids, flavonoids, chlorophylls, phenolic compounds and anti-oxidant activity in fresh and cooked broccoli (Brassica oleracea var Avenger) and cauliflower (Brassica oleracea var. Alphina F1). Lebensm. Wiss. Technol., 2015, 63(1), 177-183.
Ferreres, F.; Valentão, P.; Llorach, R.; Pinheiro, C.; Cardoso, L.; Pereira, J.A.; Sousa, C.; Seabra, R.M.; Andrade, P.B. Phenolic compounds in external leaves of tronchuda cabbage (Brassica oleracea L. var. costata DC). J. Agric. Food Chem., 2005, 53(8), 2901-2907.
[] [PMID: 15826037]
Huynh, N.T.; Smagghe, G.; Gonzales, G.B.; Van Camp, J.; Raes, K. Enzyme-assisted extraction enhancing the phenolic release from cauliflower (Brassica oleracea L. var. botrytis) outer leaves. J. Agric. Food Chem., 2014, 62(30), 7468-7476.
[] [PMID: 24992645]
Abu-Reidah, I.M.; Arráez-Roman, D.; Quirantes-Pine, R.; Fernández-Arroyo, S.; Segura-Carretero, A.; Fernandez-Gutierrez, A. HPLC–ESI-Q-TOF-MS for a comprehensive characterization of bioactive phenolic compounds in cucumber whole fruit extract. Food Res. Int., 2012, 46(1), 108-117.
Im, H.W.; Suh, B.S.; Lee, S.U.; Kozukue, N.; Ohnisi-Kameyama, M.; Levin, C.E.; Friedman, M. Analysis of phenolic compounds by high-performance liquid chromatography and liquid chromatography/mass spectrometry in potato plant flowers, leaves, stems, and tubers and in home-processed potatoes. J. Agric. Food Chem., 2008, 56(9), 3341-3349.
[] [PMID: 18386928]
Kumar, B.R. A Review on metabolic engineering approaches for enrichment and production of new secondary metabolites in Basella species. World J. Pharm. Pharm. Sci., 2016, 5(4), 652-671.
Nichenametla, S.N.; Taruscio, T.G.; Barney, D.L.; Exon, J.H. A review of the effects and mechanisms of polyphenolics in cancer. Crit. Rev. Food Sci. Nutr., 2006, 46(2), 161-183.
[] [PMID: 16431408]
Carocho, M.; Ferreira, I.C.F.R. The role of phenolic compounds in the fight against cancer--a review. Anticancer. Agents Med. Chem., 2013, 13(8), 1236-1258.
[] [PMID: 23796249]
Magnani, C.; Issac, V.L.B.; Correa, M.A.; Salgado, H.R.N. Caffeic acid: a review of its potential use in medications and cosmetics. Anal. Methods, 2014, 6, 3203-3210.
Kumar, N.; Pruthi, V. Potential applications of ferulic acid from natural sources. Biotechnol. Rep. (Amst.), 2014, 4(4), 86-93.
[] [PMID: 28626667]
Guzman, J.D. Natural cinnamic acids, synthetic derivatives and hybrids with antimicrobial activity. Molecules, 2014, 19(12), 19292-19349.
[] [PMID: 25429559]
Badhani, B.; Shama, N.; Kakkar, R. Gallic acid: A versatile antioxidant with promising therapeutic and industrial applications. RSC Advances, 2015, 5, 27540-27557.
Kakkar, S.; Bais, S. A review on protocatechuic acid and its pharmacological potential. ISRN Pharmacol., 2014, 2014 952943
[] [PMID: 25006494]
Srinivasulu, C.; Ramgopal, M.; Ramanjaneyulu, G.; Anuradha, C.M.; Suresh Kumar, C. Syringic Acid (SA) ‒ A review of its occurrence, biosynthesis, pharmacological and industrial importance. Biomed. Pharmacother., 2018, 108, 547-557.
[] [PMID: 30243088]
Khan, F.; Niaz, K.; Maqbool, F.; Ismail Hassan, F.; Abdollahi, M.; Nagulapalli Venkata, K.C.; Nabavi, S.M.; Bishayee, A. Molecular targets underlying the anticancer effects of quercetin: An update. Nutrients, 2016, 8(9), 1-19.
[] [PMID: 27589790]
Devi, K.P.; Rajavel, T.; Habtemariam, S.; Nabavi, S.F.; Nabavi, S.M. Molecular mechanisms underlying anticancer effects of myricetin. Life Sci., 2015, 142, 19-25.
[] [PMID: 26455550]
Lin, Y.; Shi, R.; Wang, X.; Shen, H.M. Luteolin, a flavonoid with potential for cancer prevention and therapy. Curr. Cancer Drug Targets, 2008, 8(7), 634-646.
[] [PMID: 18991571]
Zhou, X.; Wang, F.; Zhou, R.; Song, X.; Xie, M. Apigenin: A current review on its beneficial biological activities. J. Food Biochem., 2016, 41(4), 1-11.
Calderón-Montaño, J.M.; Burgos-Morón, E.; Pérez-Guerrero, C.; López-Lázaro, M. A review on the dietary flavonoid kaempferol. Mini Rev. Med. Chem., 2011, 11(4), 298-344.
[] [PMID: 21428901]
Rao, V.P.; Kiran, S.D.V.S.; Rohini, P.; Bhagyasree, P. Flavonoid: A review on Naringenin. J. Pharmacogn. Phytochem., 2017, 6(5), 2278-2783.
Hee Park, M.; Kim, S.; Song, Y.; Kim, S.; Hyung-Joon, K.; Hee Sam, N.; Chung, J. Rutin induces autophagy in cancer cells. Int. J. Oral Biol., 2016, 41(1), 45-51.
Rosa, L.S.; Silva, N.J.A.; Soares, N.C.P.; Monteiro, M.C.; Teodoro, A.J. Anticancer properties of phenolic acids in colon cancer – A review. J. Nutr. Food Sci., 2016, 6(2), 1-7.
Naczk, M.; Shahidi, F. Phenolics in cereals, fruits and vegetables: Occurrence, extraction and analysis. J. Pharm. Biomed. Anal., 2006, 41(5), 1523-1542.
[] [PMID: 16753277]
Działo, M.; Mierziak, J.; Korzun, U.; Preisner, M.; Szopa, J.; Kulma, A. The potential of plant phenolics in prevention and therapy of skin disorders. Int. J. Mol. Sci., 2016, 17(2), 160.
[] [PMID: 26901191]
Liu, R.H. Potential synergy of phytochemicals in cancer prevention: mechanism of action. J. Nutr., 2004, 134(12)(Suppl.), 3479S-3485S.
[] [PMID: 15570057]
Padmavati, M.; Sakthivel, N.; Thara, K.V.; Reddy, A.R. Differential sensitivity of rice pathogens to growth inhibition by flavonoids. Phytochemistry, 1997, 46(3), 499-502.
Lwashina, T. The Structure and distribution of the flavonoids in plants. J. Plant Res., 2000, 113(3), 287-299.
Thilakarathna, S.H.; Rupasinghe, H.P.V. Flavonoid bioavailability and attempts for bioavailability enhancement. Nutrients, 2013, 5(9), 3367-3387.
[] [PMID: 23989753]
Lafay, S.; Gil-Izquierdo, A. Bioavailability of phenolic acids. Phytochem. Rev., 2008, 7, 301-311.
Olthof, M.R.; Hollman, P.C.H.; Katan, M.B. Chlorogenic acid and caffeic acid are absorbed in humans. J. Nutr., 2001, 131(1), 66-71.
[] [PMID: 11208940]
Graefe, E.U.; Wittig, J.; Mueller, S.; Riethling, A.K.; Uehleke, B.; Drewelow, B.; Pforte, H.; Jacobasch, G.; Derendorf, H.; Veit, M. Pharmacokinetics and bioavailability of quercetin glycosides in humans. J. Clin. Pharmacol., 2001, 41(5), 492-499.
[] [PMID: 11361045]
Donaldson, M.S. Nutrition and cancer: A review of the evidence for an anti-cancer diet. Nutr. J., 2004, 19(3), 1-21.
[] [PMID: 526387]
Palmer, S. Diet, nutrition and cancer. Prog. Food Nutr. Sci., 1985, 9(3-4), 283-341.
[PMID: 3010379]
Liu, R.H. Health-promoting components of fruits and vegetables in the diet. Adv. Nutr., 2013, 4(3), 384S-392S.
[] [PMID: 23674808]
Wahle, K.W.J.; Brown, I.; Rotondo, D.; Heys, S.D. Plant phenolics in the prevention and treatment of cancer. Adv. Exp. Med. Biol., 2010, 698, 36-51.
[] [PMID: 21520702]
Russo, G.L. Ins and outs of dietary phytochemicals in cancer chemoprevention. Biochem. Pharmacol., 2007, 74(4), 533-544.
[] [PMID: 17382300]
Chen, H.M.; Wu, Y.C.; Chia, Y.C.; Chang, F.R.; Hsu, H.K.; Hsieh, Y.C.; Chen, C.C.; Yuan, S.S. Gallic acid, a major component of Toona sinensis leaf extracts, contains a ROS-mediated anti-cancer activity in human prostate cancer cells. Cancer Lett., 2009, 286(2), 161-171.
[] [PMID: 19589639]
Kawada, M.; Ohno, Y.; Ri, Y.; Ikoma, T.; Yuugetu, H.; Asai, T.; Watanabe, M.; Yasuda, N.; Akao, S.; Takemura, G.; Minatoguchi, S.; Gotoh, K.; Fujiwara, H.; Fukuda, K. Anti-tumor effect of gallic acid on LL-2 lung cancer cells transplanted in mice. Anticancer Drugs, 2001, 12(10), 847-852.
[] [PMID: 11707653]
Umesalma, S.; Nagendraprabhu, P.; Sudhandiran, G. Ellagic acid inhibits proliferation and induced apoptosis via the Akt signaling pathway in HCT-15 colon adenocarcinoma cells. Mol. Cell. Biochem., 2015, 399(1-2), 303-313.
[] [PMID: 25355159]
Yin, M.C.; Lin, C.C.; Wu, H.C.; Tsao, S.M.; Hsu, C.K. Apoptotic effects of protocatechuic acid in human breast, lung, liver, cervix, and prostate cancer cells: potential mechanisms of action. J. Agric. Food Chem., 2009, 57(14), 6468-6473.
[] [PMID: 19601677]
Jaganathan, S.K.; Supriyanto, E.; Mandal, M. Events associated with apoptotic effect of p-Coumaric acid in HCT-15 colon cancer cells. World J. Gastroenterol., 2013, 19(43), 7726-7734.
[] [PMID: 24282361]
Zhu, B.; Shang, B.; Li, Y.; Zhen, Y. Inhibition of histone deacetylases by trans-cinnamic acid and its antitumor effect against colon cancer xenografts in athymic mice. Mol. Med. Rep., 2016, 13(5), 4159-4166.
[] [PMID: 27035417]
Ahn, C.H.; Choi, W.C.; Kong, J.Y. Chemosensitizing activity of caffeic acid in multidrug-resistant MCF-7/Dox human breast carcinoma cells. Anticancer Res., 1997, 17(3C), 1913-1917.
[PMID: 9216644]
Zhang, X.; Lin, D.; Jiang, R.; Li, H.; Wan, J.; Li, H. Ferulic acid exerts antitumor activity and inhibits metastasis in breast cancer cells by regulating epithelial to mesenchymal transition. Oncol. Rep., 2016, 36(1), 271-278.
[] [PMID: 27177074]
Shan, B.E.; Wang, M.X.; Li, R.Q. Quercetin inhibit human SW480 colon cancer growth in association with inhibition of cyclin D1 and survivin expression through Wnt/β-catenin signaling pathway. Cancer Invest., 2009, 27(6), 604-612.
[] [PMID: 19440933]
Dihal, A.A.; van der Woude, H.; Hendriksen, P.J.; Charif, H.; Dekker, L.J.; Ijsselstijn, L.; de Boer, V.C.J.; Alink, G.M.; Burgers, P.C.; Rietjens, I.M.C.M.; Woutersen, R.A.; Stierum, R.H. Transcriptome and proteome profiling of colon mucosa from quercetin fed F344 rats point to tumor preventive mechanisms, increased mitochondrial fatty acid degradation and decreased glycolysis. Proteomics, 2008, 8(1), 45-61.
[] [PMID: 18095365]
Li, W.; Du, B.; Wang, T.; Wang, S.; Zhang, J. Kaempferol induces apoptosis in human HCT116 colon cancer cells via the Ataxia-Telangiectasia mutated-p53 pathway with the involvement of p53 upregulated modulator of apoptosis. Chem. Biol. Interact., 2009, 177(2), 121-127.
[] [PMID: 19028473]
Way, T.D.; Kao, M.C.; Lin, J.K. Apigenin induces apoptosis through proteasomal degradation of HER2/neu in HER2/neu-overexpressing breast cancer cells via the phosphatidylinositol 3-kinase/Akt-dependent pathway. J. Biol. Chem., 2004, 279(6), 4479-4489.
[] [PMID: 14602723]
Shukla, S.; Fu, P.; Gupta, S. Apigenin induces apoptosis by targeting inhibitor of apoptosis proteins and Ku70-Bax interaction in prostate cancer. Apoptosis, 2014, 19(5), 883-894.
[] [PMID: 24563225]
Kang, N.J.; Shin, S.H.; Lee, H.J.; Lee, K.W. Polyphenols as small molecular inhibitors of signaling cascades in carcinogenesis. Pharmacol. Ther., 2011, 130(3), 310-324.
[] [PMID: 21356239]
Sun, D.W.; Zhang, H.D.; Mao, L.; Mao, C.F.; Chen, W.; Cui, M.; Ma, R.; Cao, H.X.; Jing, C.W.; Wang, Z.; Wu, J.Z.; Tang, J.H. Luteolin inhibits breast cancer development and progression in vitro and in vivo by suppressing notch signaling and regulating miRNAs. Cell. Physiol. Biochem., 2015, 37(5), 1693-1711.
[] [PMID: 26545287]
Zhang, S.; Wang, L.; Liu, H.; Zhao, G.; Ming, L. Enhancement of recombinant myricetin on the radiosensitivity of lung cancer A549 and H1299 cells. Diagn. Pathol., 2014, 9(9), 68.
[] [PMID: 24650056]
Alonso-Castro, A.J.; Domínguez, F.; García-Carrancá, A. Rutin exerts antitumor effects on nude mice bearing SW480 tumor. Arch. Med. Res., 2013, 44(5), 346-351.
[] [PMID: 23867787]
Sequetto, P.L.; Oliveira, T.T.; Maldonado, I.R.S.C.; Augusto, L.E.F.; Mello, V.J.; Pizziolo, V.R.; Almeida, M.R.; Silva, M.E.; Novaes, R.D. Naringin accelerates the regression of pre-neoplastic lesions and the colorectal structural reorganization in a murine model of chemical carcinogenesis. Food Chem. Toxicol., 2014, 64, 200-209.
[] [PMID: 24296135]
Nalini, N.; Aranganathan, S.; Kabalimurthy, J. Chemopreventive efficacy of hesperetin (citrus flavonone) against 1,2-dimethylhydrazine-induced rat colon carcinogenesis. Toxicol. Mech. Methods, 2012, 22(5), 397-408.
[] [PMID: 22409373]
Suzuki, K.; Koike, H.; Matsui, H.; Ono, Y.; Hasumi, M.; Nakazato, H.; Okugi, H.; Sekine, Y.; Oki, K.; Ito, K.; Yamamoto, T.; Fukabori, Y.; Kurokawa, K.; Yamanaka, H. Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC-3. Int. J. Cancer, 2002, 99(6), 846-852.
[] [PMID: 12115487]
Hafeez, B.B.; Siddiqui, I.A.; Asim, M.; Malik, A.; Afaq, F.; Adhami, V.M.; Saleem, M.; Din, M.; Mukhtar, H. A dietary anthocyanidin delphinidin induces apoptosis of human prostate cancer PC3 cells in vitro and in vivo: Involvement of nuclear factor-kappaB signaling. Cancer Res., 2008, 68(20), 8564-8572.
[] [PMID: 18922932]
Liao, H.F.; Chen, Y.Y.; Liu, J.J.; Hsu, M.L.; Shieh, H.J.; Liao, H.J.; Shieh, C.J.; Shiao, M.S.; Chen, Y.J. Inhibitory effect of caffeic acid phenethyl ester on angiogenesis, tumor invasion, and metastasis. J. Agric. Food Chem., 2003, 51(27), 7907-7912.
[] [PMID: 14690372]
Chiang, E.P.; Tsai, S.Y.; Kuo, Y.H.; Pai, M.H.; Chiu, H.L.; Rodriguez, R.L.; Tang, F.Y. Caffeic acid derivatives inhibit the growth of colon cancer: involvement of the PI3-K/Akt and AMPK signaling pathways. PLoS One, 2014, 9(6) e99631
[] [PMID: 24960186 ]
Ozturk, G.; Ginis, Z.; Akyol, S.; Erden, G.; Gurel, A.; Akyol, O. The anticancer mechanism of caffeic acid phenethyl ester (CAPE): review of melanomas, lung and prostate cancers. Eur. Rev. Med. Pharmacol. Sci., 2012, 16(15), 2064-2068.
[PMID: 23280020]
Rocha, L.D.; Monteiro, M.C.; Junger Teodoro, A. Anticancer properties of hydroxycinnamic acids-A review. Cancer Clin. Oncol., 2012, 1(2), 109-121.
Tsai, C.M.; Sun, F.M.; Chen, Y.L.; Hsu, C.L.; Yen, G.C.; Weng, C.J. Molecular mechanism depressing PMA-induced invasive behaviors in human lung adenocarcinoma cells by cis- and trans-cinnamic acid. Eur. J. Pharm. Sci., 2013, 48(3), 494-501.
[] [PMID: 23228413]
Wu, Z.R.; Liu, J.; Li, J.Y.; Zheng, L.F.; Li, Y.; Wang, X.; Xie, Q.J.; Wang, A.X.; Li, Y.H.; Liu, R.H.; Li, H.Y. Synthesis and biological evaluation of hydroxycinnamic acid hydrazide derivatives as inducer of caspase-3. Eur. J. Med. Chem., 2014, 85, 778-783.
[] [PMID: 25147141]
Szliszka, E.; Czuba, Z.P.; Bronikowska, J.; Mertas, A.; Paradysz, A.; Krol, W. Ethanolic extract of propolis augments TRAIL-induced apoptotic death in prostate cancer cells. Evid. Based Complement. Alternat. Med., 2011, 2011 535172
[] [PMID: 19892808]
Saravanan, R.; Pemaiah, B.; Sridharan, S.; Narayanan, M.; Ramalingam, S. Enhanced cytotoxic potential of Orthosiphon stamineus extract in MCF-7 cells through suppression of nucleolin and BCL2. Bangladesh J. Pharmacol., 2017, 12(3), 268-275.
Sen, A.; Atmaca, P.; Terzioglu, G.; Arslan, S. Anticarcinogenic effect and carcinogenic potential of the dietary phenolic acid: O-coumaric acid. Nat. Prod. Commun., 2013, 8(9), 1269-1274.
[] [PMID: 24273864]
Peng, W.; Wu, J.G.; Jiang, Y.B.; Liu, Y.J.; Sun, T.; Wu, N.; Wu, C.J. Antitumor activity of 4-O-(2″-O-acetyl-6″-O-p-coumaroyl-β-D-glucopyranosyl)-p-coumaric acid against lung cancers via mitochondrial-mediated apoptosis. Chem. Biol. Interact., 2015, 233, 8-13.
[] [PMID: 25824411]
Tsai, C.M.; Yen, G.C.; Sun, F.M.; Yang, S.F.; Weng, C.J. Assessment of the anti-invasion potential and mechanism of select cinnamic acid derivatives on human lung adenocarcinoma cells. Mol. Pharm., 2013, 10(5), 1890-1900.
[] [PMID: 23560439]
Eroğlu, C.; Seçme, M.; Bağcı, G.; Dodurga, Y. Assessment of the anticancer mechanism of ferulic acid via cell cycle and apoptotic pathways in human prostate cancer cell lines. Tumour Biol., 2015, 36(12), 9437-9446.
[] [PMID: 26124008]
Subramanian, A.P.; John, A.A.; Vellayappan, M.V.; Balaji, A.; Jaganathan, S.K.; Supriyanto, E.; Yusof, M. Gallic acid: Prospects and molecular mechanisms of its anticancer activity. RSC Advances, 2015, 5(45), 35608-35621.
You, B.R.; Park, W.H. Gallic acid-induced lung cancer cell death is related to glutathione depletion as well as reactive oxygen species increase. Toxicol. In Vitro, 2010, 24(5), 1356-1362.
[] [PMID: 20417267]
Zheng, Q.; Hirose, Y.; Yoshimi, N.; Murakami, A.; Koshimizu, K.; Ohigashi, H.; Sakata, K.; Matsumoto, Y.; Sayama, Y.; Mori, H. Further investigation of the modifying effect of various chemopreventive agents on apoptosis and cell proliferation in human colon cancer cells. J. Cancer Res. Clin. Oncol., 2002, 128(10), 539-546.
[] [PMID: 12384797]
Orabi, K.Y.; Abaza, M.S.; El Sayed, K.A.; Elnagar, A.Y.; Al-Attiyah, R.; Guleri, R.P. Selective growth inhibition of human malignant melanoma cells by syringic acid-derived proteasome inhibitors. Cancer Cell Int., 2013, 13(1), 82.
[] [PMID: 23958424]
Abaza, M.S.; Al-Attiyah, R.; Bhardwaj, R.; Abbadi, G.; Koyippally, M.; Afzal, M. Syringic acid from Tamarix aucheriana possesses antimitogenic and chemo-sensitizing activities in human colorectal cancer cells. Pharm. Biol., 2013, 51(9), 1110-1124.
[] [PMID: 23745612]
Karthik, G.; Vijayakumar, A.; Natarajapillai, S. Preliminary study on salubrious effect of syringic acid on apoptosis in human lung carcinoma A549 cells and in silico analysis through docking studies. Asian J Pharm Clin Res., 2014, 7(1), 46-49.
Wang, L.S.; Stoner, G.D. Anthocyanins and their role in cancer prevention. Cancer Lett., 2008, 269(2), 281-290.
[] [PMID: 18571839]
Ha, U.S.; Bae, W.J.; Kim, S.J.; Yoon, B.I.; Hong, S.H.; Lee, J.Y.; Hwang, T.K.; Hwang, S.Y.; Wang, Z.; Kim, S.W. Anthocyanin induces apoptosis of DU-145 cells in vitro and inhibits xenograft growth of prostate cancer. Yonsei Med. J., 2015, 56(1), 16-23.
[] [PMID: 25510742]
Srivastava, A.; Akoh, C.C.; Fischer, J.; Krewer, G. Effect of anthocyanin fractions from selected cultivars of Georgia-grown blueberries on apoptosis and phase II enzymes. J. Agric. Food Chem., 2007, 55(8), 3180-3185.
[] [PMID: 17381106]
Reddivari, L.; Vanamala, J.; Chintharlapalli, S.; Safe, S.H.; Miller, J.C., Jr Anthocyanin fraction from potato extracts is cytotoxic to prostate cancer cells through activation of caspase-dependent and caspase-independent pathways. Carcinogenesis, 2007, 28(10), 2227-2235.
[] [PMID: 17522067]
Fernandes, I.; Faria, A.; Azevedo, J.; Soares, S.; Calhau, C.; De Freitas, V.; Mateus, N. Influence of anthocyanins, derivative pigments and other catechol and pyrogallol-type phenolics on breast cancer cell proliferation. J. Agric. Food Chem., 2010, 58(6), 3785-3792.
[] [PMID: 20170107]
Chen, P.N.; Chu, S.C.; Chiou, H.L.; Kuo, W.H.; Chiang, C.L.; Hsieh, Y.S. Mulberry anthocyanins, cyanidin 3-rutinoside and cyanidin 3-glucoside, exhibited an inhibitory effect on the migration and invasion of a human lung cancer cell line. Cancer Lett., 2006, 235(2), 248-259.
[] [PMID: 15975709]
Salmani, J.M.M.; Xiao-Pingo, Z.; Jacob, J.A.; Bao-An, C. Apigenin’s anticancer properties and molecular mechanisms of action:Recent advances and future prospectives Chin. J. Nat. Med.,, 2017, 15(5), 0321-0329.
Seeram, N.P.; Zhang, Y.; Nair, M.G. Inhibition of proliferation of human cancer cells and cyclooxygenase enzymes by anthocyanidins and catechins. Nutr. Cancer, 2003, 46(1), 101-106.
[] [PMID: 12925310]
Shimizu, M.; Deguchi, A.; Lim, J.T.; Moriwaki, H.; Kopelovich, L.; Weinstein, I.B. (-)-Epigallocatechin gallate and polyphenon E inhibit growth and activation of the epidermal growth factor receptor and human epidermal growth factor receptor-2 signaling pathways in human colon cancer cells. Clin. Cancer Res., 2005, 11(7), 2735-2746.
[] [PMID: 15814656]
Adhami, V.M.; Ahmad, N.; Mukhtar, H. Molecular targets for green tea in prostate cancer prevention. J. Nutr., 2003, 133(7)(Suppl.), 2417S-2424S.
[] [PMID: 12840218]
Uifălean, A.; Schneider, S.; Ionescu, C.; Lalk, M.; Iuga, C.A. Soy isoflavones and breast cancer cell lines: Molecular mechanisms and future perspectives. Molecules, 2015, 21(1) E13
[] [PMID: 26703550]
Kuntz, S.; Wenzel, U.; Daniel, H. Comparative analysis of the effects of flavonoids on proliferation, cytotoxicity, and apoptosis in human colon cancer cell lines. Eur. J. Nutr., 1999, 38(3), 133-142.
[] [PMID: 10443335]
Lian, F.; Bhuiyan, M.; Li, Y.W.; Wall, N.; Kraut, M.; Sarkar, F.H. Genistein-induced G2-M arrest, p21WAF1 upregulation, and apoptosis in a non-small-cell lung cancer cell line. Nutr. Cancer, 1998, 31(3), 184-191.
[] [PMID: 9795970]
Onozawa, M.; Fukuda, K.; Ohtani, M.; Akaza, H.; Sugimura, T.; Wakabayashi, K. Effects of soybean isoflavones on cell growth and apoptosis of the human prostatic cancer cell line LNCaP. Jpn. J. Clin. Oncol., 1998, 28(6), 360-363.
[] [PMID: 9730149]
Kim, S.H.; Choi, K.C. Anti-cancer effect and underlying mechanism(s) of kaempferol, a phytoestrogen, on the regulation of apoptosis in diverse cancer cell models. Toxicol. Res., 2013, 29(4), 229-234.
[] [PMID: 24578792]
Sara, J.C.; Lopez, S.; Abia, R.; Rocio, R.A.; Jimenez, A.; Guillen, R.; Muriana, F.J.G. Combination of quercetin and kaempferol enhances in vitro cytotoxicity on human colon cancer (HCT-116). Cells Rec. Nat. Prod., 2014, 8(3), 262-271.
Cho, H.J.; Park, J.H.Y. Kaempferol induces cell cycle arrest in HT-29 human colon cancer cells. J. Cancer Prev., 2013, 18(3), 257-263.
[] [PMID: 25337553]
Halimah, E.; Diantini, A.; Destiani, D.P.; Pradipta, I.S.; Sastramihardja, H.S.; Lestari, K.; Subarnas, A.; Abdulah, R.; Koyama, H. Induction of caspase cascade pathway by kaempferol-3-O-rhamnoside in LNCaP prostate cancer cell lines. Biomed. Rep., 2015, 3(1), 115-117.
[] [PMID: 25469259]
Zhao, Y.; Yang, G.; Ren, D.; Zhang, X.; Yin, Q.; Sun, X. Luteolin suppresses growth and migration of human lung cancer cells. Mol. Biol. Rep., 2011, 38(2), 1115-1119.
[] [PMID: 20589534]
Tuorkey, M.J. Molecular targets of luteolin in cancer. Eur. J. Cancer Prev., 2016, 25(1), 65-76.
[] [PMID: 25714651]
Yadegarynia, S.; Pham, A.; Ng, A.; Nguyen, D.; Lialiutska, T.; Bortolazzo, A.; Sivryuk, V.; Bremer, M.; White, J.B. Profiling flavonoid cytotoxicity in human breast cancer cell lines: Determination of structure-function relationships. Nat. Prod. Commun., 2014, 9(5), 597-606.
[] [PMID: 25026697]
Xu, R.; Zhang, Y.; Ye, X.; Xue, S.; Shi, J.; Pan, J.; Chen, Q. Inhibition effects and induction of apoptosis of flavonoids on the prostate cancer cell line PC-3 in vitro. Food Chem., 2013, 138(1), 48-53.
[] [PMID: 23265454]
Bulzomi, P.; Bolli, A.; Galluzzo, P.; Acconcia, F.; Ascenzi, P.; Marino, M. The naringenin-induced proapoptotic effect in breast cancer cell lines holds out against a high bisphenol a background. IUBMB Life, 2012, 64(8), 690-696.
[] [PMID: 22692793]
Yoon, H.; Kim, T.W.; Shin, S.Y.; Park, M.J.; Yong, Y.; Kim, D.W.; Islam, T.; Lee, Y.H.; Jung, K.Y.; Lim, Y. Design, synthesis and inhibitory activities of naringenin derivatives on human colon cancer cells. Bioorg. Med. Chem. Lett., 2013, 23(1), 232-238.
[] [PMID: 23177257]
Chang, H.L.; Chang, Y.M.; Lai, S.C.; Chen, K.M.; Wang, K.C.; Chiu, T.T.; Chang, F.H.; Hsu, L.S. Naringenin inhibits migration of lung cancer cells via the inhibition of matrix metalloproteinases-2 and -9. Exp. Ther. Med., 2017, 13(2), 739-744.
[] [PMID: 28352360]
Lim, W.; Park, S.; Bazer, F.W.; Song, G. Naringenin-induced apoptotic cell death in prostate cancer cells is mediated via the PI3K/AKT and MAPK signaling pathways. J. Cell. Biochem., 2017, 118(5), 1118-1131.
[] [PMID: 27606834]
Gibellini, L.; Pinti, M.; Nasi, M.; Montagna, J.P.; De Biasi, S.; Roat, E.; Bertoncelli, L.; Cooper, E.L.; Cossarizza, A. Quercetin and cancer chemoprevention. Evid. Based Complement. Alternat. Med., 2011, 2011 591356
[] [PMID: 21792362]
Xiao-hua, L.; Zhi-yi, L.; Gu, Y.; Zhe, L.; Chen, Y.; Gao, H. Expression of NF-kappaB and p38 under intervention of rutin in lung cancer therapy. Biomed. Res. (Aligarh), 2017, 28(5), 2344-2347.
Perk, A.A.; Shatynska-Mytsyk, I.; Gerçek, Y.C.; Boztaş, K.; Yazgan, M.; Fayyaz, S.; Farooqi, A.A. Rutin mediated targeting of signaling machinery in cancer cells. Cancer Cell Int., 2014, 14(1), 124.
[] [PMID: 25493075]
Ahmad, M. Sahabjada; Akhtar, J.; Hussain, A.; Badaruddeen; Arshad, M.; Mishra, A. Development of a new rutin nanoemulsion and its application on prostate carcinoma PC3 cell line. EXCLI J., 2017, 16, 810-823.
[PMID: 28694767]

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Year: 2020
Published on: 09 April, 2020
Page: [29 - 48]
Pages: 20
DOI: 10.2174/1871520619666191019112712
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