Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Review Article

Crocetin and Crocin from Saffron in Cancer Chemotherapy and Chemoprevention

Author(s): Alessandro Colapietro, Andrea Mancini, Anna Maria D'Alessandro and Claudio Festuccia*

Volume 19, Issue 1, 2019

Page: [38 - 47] Pages: 10

DOI: 10.2174/1871520619666181231112453

Price: $65

Abstract

Introduction: Cancer is a disorder which has a powerful impact on the quality life and life expectancy despite the increase in drugs and treatments available for cancer patients. Moreover, many new therapeutic options are known to have adverse reactions without any improvement in outcome than before. Nowadays, natural products or plant derivatives are used as chemoprevention drugs and chemotherapy is the new approach that uses specific cell premalignant transformation in the malignant form. Natural substances derived from plants, such as polyphenols, flavonoids, carotenoids, alkaloids and others, can be biologically active and have a wide spectrum of effects. The protective effects of Saffron carotenoids (crocin and crocetin) have been extensively studied mainly for their antioxidant properties, however, they have various other biological activities including tumor growth inhibition with the induction of cell death.

Methods: The relevant information on Saffron and its carotenoids was collected from scientific databases (such as PubMed, Web of Science, Science Direct). To identify all published articles in relation to saffron, crocin and crocetin, in different types of cancer, no language restriction has been used.

Results: To date, crossing the words saffron and cancer, approximately 150 articles can be found. If crossing is made between crocin and cancer, approximately 60 articles can be found. With the crossing between crocetin and cancer, the number is approximately 55, while between carotenoids and cancer, the number exceeds 16.000 reports. In all the papers published to date, there are evidences that saffron and its carotenoids exert chemopreventive activity through anti-oxidant activity, cancer cells apoptosis, inhibition of cell proliferation, enhancement of cell differentiation, modulation of cell cycle progression and cell growth, modulation of tumor metabolism, stimulation of cell-to-cell communication and immune modulation.

Conclusion: Here, we have tried to offer an up-to-date overview of pre-clinical experimental investigations on the potential use of the main carotenoids of saffron in tumor models and focus the attention on the molecular mechanisms involved.

Keywords: Saffron, crocetin, crocin, cancer, premalignant transformation, antioxidant.

Graphical Abstract
[1]
Brown, J.C.; Winters-Stone, K.; Lee, A.; Schmitz, K.H. Cancer, physical activity, and exercise. Compr. Physiol., 2012, 2, 2775-2809.
[2]
Lee, J.K.; So, K.A.; Piyathilake, C.J.; Kim, M.K. Mild obesity, physical activity, calorie intake, and the risks of cervical intraepithelial neoplasia and cervical cancer. PLoS One, 2013, 8, e66555.
[3]
Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin., 2015, 65, 87-108.
[4]
Chang, J.C. Cancer stem cells: Role in tumor growth, recurrence, metastasis, and treatment resistance. Medicine (Baltimore), 2016, 95, S20-S25.
[5]
Richardson, J.L.; Marks, G.; Levine, A. The influence of symptoms of disease and side effects of treatment on compliance with cancer therapy. J. Clin. Oncol., 1988, 6, 1746-1752.
[6]
Baena, R.R.; Salinas, H.P. Cancer chemoprevention by dietary phytochemicals: Epidemiological evidence. Maturitas, 2016, 94, 13-19.
[7]
Greenlee, H. Natural products for cancer prevention. Semin. Oncol. Nurs., 2012, 28, 29-44.
[8]
Lee, B.M.; Park, K.K. Benefical and adverse effects of chemopreventive agents. Mutat. Res., 2003, 523-524, 265-278.
[9]
Finkel, T.; Serrano, M.; Blasco, M.A. The common biology of cancer and ageing. Nature, 2007, 448, 767-774.
[10]
Vitale, G.; Salvioli, S.; Franceschi, C. Oxidative stress and the ageing endocrine system. Nat. Rev. Endocrinol., 2013, 9, 228-240.
[11]
Yang, Y.; Karakhanova, S.; Hartwig, W.; D’Haese, J.G.; Philippov, P.P.; Werner, J.; Bazhin, A.V. Mitochondria and mitochondrial ROS in cancer: Novel targets for anticancer therapy. J. Cell. Physiol., 2016, 231, 2570-2581.
[12]
Smetana, K., Jr; Lacina, L.; Szabo, P.; Dvořánková, B.; Brož, P.; Šedo, A. Ageing as an important risk factor for cancer. Anticancer Res., 2016, 36(10), 5009-5017.
[13]
Costa, A.; Scholer-Dahirel, A.; Mechta-Grigoriou, F. The role of reactive oxygen species and metabolism on cancer cells and their microenvironment. Semin. Cancer Biol., 2014, 25, 23-32.
[14]
Du, Y.; Long, Q.; Zhang, L.; Shi, Y.; Liu, X.; Li, X.; Guan, B.; Tian, Y.; Wang, X.; Li, L.; He, D. Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling. Int. J. Oncol., 2015, 47, 2064-2072.
[15]
Fiaschi, T.; Marini, A.; Giannoni, E.; Taddei, M.L.; Gandellini, P.; De-Donatis, A.; Lanciotti, M.; Serni, S.; Cirri, P.; Chiarugi, P. Reciprocal metabolic reprogramming through lactate shuttle coordinately influences tumor-stroma interplay. Cancer Res., 2012, 72, 5130-5140.
[16]
Martinez-Outschoorn, U.E.; Lisanti, M.P.; Sotgia, F. Catabolic cancer-associated fibroblasts transfer energy and biomass to anabolic cancer cells, fueling tumor growth. Semin. Cancer Biol., 2014, 25, 47-60.
[17]
Lisanti, M.P.; Martinez-Outschoorn, U.E.; Lin, Z.; Pavlides, S.; Whitaker-Menezes, D.; Pestell, R.G.; Howell, A.; Sotgia, F. Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis: the seed and soil also needs “fertilizer”. Cell Cycle, 2011, 10, 2440-2449.
[18]
Pereira, E.J.; Smolko, C.M.; Janes, K.A. Computational models of reactive oxygen species as metabolic byproducts and signal-transduction modulators. Front. Pharmacol., 2016, 7, 457.
[19]
Williams, J.; Smith, F.; Kumar, S.; Vijayan, M.; Reddy, P.H. Are microRNAs true sensors of ageing and cellular senescence? Ageing Res. Rev., 2016, 35(16), 350-363.
[20]
Bhatti, J.S.; Bhatti, G.K.; Reddy, P.H. Mitochondrial dysfunction and oxidative stress in metabolic disorders - A step towards mitochondria based therapeutic strategies. Biochim. Biophys. Acta, 2017, 1863(16), 1066-1077.
[21]
Liu, R.H. Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am. J. Clin. Nutr., 2003, 78, 517S-520S.
[22]
Carmona, M.; Zalacain, A.; Salinas, M.R.; Alonso, G.L. A new approach to saffron aroma. Crit. Rev. Food Sci. Nutr., 2007, 47, 145-159.
[23]
Aviram, M.; Dornfeld, L.; Kaplan, M.; Coleman, R.; Gaitini, D.; Nitecki, S.; Hofman, A.; Rosenblat, M.; Volkova, N.; Presser, D.; Attias, J.; Hayek, T.; Fuhrman, B. Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular diseases: studies in atherosclerotic mice and in humans. Drugs Exp. Clin. Res., 2002, 28, 49-62.
[24]
Vislocky, L.M.; Fernandez, M.L. Biomedical effects of grape products. Nutr. Rev., 2010, 68(11), 656-670.
[25]
Bolhassani, A.; Khavari, A.; Bathaie, S.Z. Saffron and natural carotenoids: Biochemical activities and anti-tumor effects. Biochim. Biophys. Acta, 2014, 184, 20-30.
[26]
Bathaie, S.Z.; Farajzade, A.; Hoshyar, R. A review of the chemistry and uses of crocins and crocetin, the carotenoid natural dyes in saffron, with particular emphasis on applications as colorants including their use as biological stains. Biotech. Histochem., 2014, 89, 401-411.
[27]
Milani, A.; Basirnejad, M.; Shahbazi, S.; Bolhassani, A. Carotenoids: Biochemistry, pharmacology and treatment. Br. J. Pharmacol., 2016, 174(11), 1290-1324.
[28]
Leja, K.B.; Czaczyk, K. The industrial potential of herbs and spices - A mini review. Acta Sci. Pol. Technol. Aliment., 2016, 15, 353-365.
[29]
Kafi, M.; Kakhki, H.A.; Karbasi, A. Historical background, economy, acreage, production, yield and uses. Saffron (Crocus Sativus) production and processing. Enfield, NH. Science, 2006, 1-13.
[30]
Licón, C.C.; Carmona, M.; Molina, A.; Berruga, M.I. Chemical, microbiological, textural, color, and sensory characteristics of pressed ewe milk cheeses with saffron (Crocus sativus L.) during ripening. J. Dairy Sci., 2012, 95, 4263-4274.
[31]
D’Archivio, A.A.; Giannitto, A.; Maggi, M.A.; Ruggieri, F. Geographical classification of Italian saffron (Crocus sativus L.) based on chemical constituents determined by high-performance liquid-chromatography and by using linear discriminant analysis. Food Chem., 2016, 212, 110-116.
[32]
Bagur, J.M.; Salinas, A.G.L.; Jiménez-Monreal, A.M.; Chaouqi, S.; Llorens, S.; Martínez-Tomé, M.; Alonso, G.L. Saffron: An old medicinal plant and a potential novel functional food. Molecules, 2017, 23(1), E30.
[33]
Jin, Y.Y.; Zhang, J.S.; Zhang, Y.; Zhang, Y.H. Studies on the intestinal absorption of crocin in rats and determination of the partition coefficient. J. China Pharm. Univ., 2004, 35, 283-284.
[34]
Asai, A.; Nakano, T.; Takahashi, M.; Nagao, A. Orally administered crocetin and crocins are absorbed into blood plasma as crocetin and its glucuronide conjugates in mice. J. Agric. Food Chem., 2005, 53, 7302-7306.
[35]
Xi, L.; Qian, Z.; Du, P.; Fu, J. Pharmacokinetic properties of crocin (crocetin digentiobiose ester) following oral administration in rats. Phytomedicine, 2007, 14, 633-636.
[36]
Umigai, N.; Murakami, K.; Ulit, M.V.; Antonio, L.S.; Shirotori, M.; Morikawa, H.; Nakano, T. The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration. Phytomedicine, 2011, 18, 575-578.
[37]
Mashmoul, M.; Azlan, A.; Yusof, B.N.M.; Khaza’ai, H.; Mohtarrudin, N.; Boroushaki, M.T. Effects of saffron extract and crocin on anthropometrical, nutritional and lipid profile parameters of rats fed a high fat diet. J. Funct. Foods, 2014, 8, 180-187.
[38]
Liu, T.Z.; Qian, Z.Y. Pharmacokinetics of crocetin in rats. Acta Pharm. Sin. B, 2002, 37, 367-369.
[39]
Chryssanthi, D.G.; Lamari, F.N.; Georgakopoulos, C.D.; Cordopatis, P. A new validated SPE-HPLC method for monitoring crocetin in human plasma-application after saffron tea consumption. J. Pharm. Biomed. Anal., 2011, 55, 563-568.
[40]
Mohammadpour, A.H.; Ramezani, M.; Anaraki, T.N.; Malaekeh-Nikouei, B.; Farzad, A.S.; Hosseinzadeh, H. Development and validation of HPLC method for determination of crocetin, a constituent of saffron, in human serum samples. Iran. J. Basic Med. Sci., 2013, 16, 47-56.
[41]
Zhang, Y.; Fei, F.; Zhen, L.; Zhu, X.; Wang, J.; Li, S.; Geng, J.; Sun, R.; Yu, X.; Chen, T.; Feng, S.; Wang, P.; Yang, N.; Zhu, Y.; Huang, J.; Zhao, Y.; Aa, J.; Wang, G. Sensitive analysis and simultaneous assessment of pharmacokinetic properties of crocin and crocetin after oral administration in rats. J. Chrom. B Analyt. Technol. Biomed. Life Sci., 2017, 1044, 1-7.
[42]
Gainer, J.L.; Wallis, D.A.; Jones, J.R. The effect of crocetin on skin papillomas and rous sarcoma. Oncology, 1976, 33, 222-224.
[43]
Abdullaev, F.I.; Frenkel, G.D. The effect of saffron on intracellular DNA, RNA and protein synthesis in malignant and non-malignant human cells. Biofactors, 1992, 4, 43-45.
[44]
Das, I.; Chakrabarty, R.N.; Das, S. Saffron can prevent chemically induced skin carcinogenesis in Swiss albino mice. Asian Pac. J. Cancer Prev., 2004, 5, 70-76.
[45]
Bolhassani, A.; Khavari, A.; Bathaie, S.Z. Saffron and natural carotenoids: Biochemical activities and anti-tumor effects. Biochim. Biophys. Acta, 2014, 1845, 20-30.
[46]
Vajravijayan, S.; Pletnev, S.; Pletnev, V.Z.; Nandhagopal, N.; Gunasekaran, K. Structural analysis of β-prism lectin from Colocasia esculenta (L.) S chott. Int. J. Biol. Macromol., 2016, 91, 518-523.
[47]
Noureini, S.K.; Wink, M. Antiproliferative effects of crocin in HepG2 cells by telomerase inhibition and hTERT down-regulation. Asian Pac. J. Cancer Prev., 2012, 13, 2305-2309.
[48]
Salomi, M.J.; Nair, S.C.; Panikkar, K.R. Inhibitory effects of Nigella sativa and saffron (Crocus sativus) on chemical carcinogenesis in mice. Nutr. Cancer, 1991, 16, 67-72.
[49]
Wang, C.J.; Lee, M.J.; Chang, M.C.; Lin, J.K. Inhibition of tumor promotion in benzo[a]pyrene-initiated CD-1 mouse skin by crocetin. Carcinogenesis, 1995, 16, 187-191.
[50]
Das, I.; Das, S.; Saha, T. Saffron suppresses oxidative stress in DMBA-induced skin carcinoma: A histopathological study. Acta Histochem., 2010, 112(4), 317-327.
[51]
Mathews-Roth, M.M. Effect of crocetin on experimental skin tumors in hairless mice. Oncology, 1982, 39, 362-364.
[52]
Song, L.; Kang, C.; Sun, Y.; Huang, W.; Liu, W.; Qian, Z. Crocetin inhibits lipopolysaccharide-induced inflammatory response in human umbilical vein endothelial cells. Cell. Physiol. Biochem., 2016, 40, 443-452.
[53]
Fenni, S.; Hammou, H.; Astier, J.; Bonnet, L.; Karkeni, E.; Couturier, C.; Tourniaire, F.; Landrier, J.F. Lycopene and tomato powder supplementation similarly inhibit high-fat diet induced obesity, inflammatory response and associated metabolic disorders. Mol. Nutr. Food Res., 2017, 61(9), 1601083.
[54]
Wang, C.J.; Lee, M.J.; Chang, M.C.; Lin, J.K. Inhibition of tumor promotion in benzo(a)pyene-initiated CD-1 mouse skin by crocetin. Carcinogenesis, 1995, 16, 187-191.
[55]
Giaccio, M. Crocetin from Saffron: An active component of an ancient spice. Clin. Rev. Food Sci. Nutr., 2004, 44, 155-172.
[56]
Abdullaev, F.I. Inhibitory effect of crocetin on intracellular nucleic acid and protein synthesis in malignant cells. Toxicol. Lett., 1994, 70, 243-251.
[57]
Escribano, J.; Alonso, G.L.; Coca-Prados, M.; Fernandez, A. Crocin saffranal and picocrocin from saffron (Crocus Sativus L.) inhibit the growth of human cancer cells in vitro. Cancer Lett., 1996, 100, 23-30.
[58]
Kanakis, C.D.; Tarantilis, P.A.; Tajmir-Riahi, H.A.; Polissiou, M.G. Interaction of tRNA with Safranal, Crocetin, and Dimethylcrocetin. J. Biomol. Struct. Dyn., 2007, 24, 537-546.
[59]
Zhong, Y.J.; Shi, F.; Zheng, X.L.; Wang, Q.; Yang, L.; Sun, H.; He, F.; Zhang, L.; Lin, Y.; Qin, Y.; Liao, L.C.; Wang, X. Crocetin induces cytotoxicity and enhances vincristine-induced cancer cell death via p53-dependent and -independent mechanisms. Acta Pharmacol. Sin., 2011, 32, 1529-1536.
[60]
Chen, B. Crocetin downregulates the proinfiammatory cytokines in methylcholantrene-induced rodent tumor model and inhibits COX-2 expression in cervical cancer cells. BioMed Res. Int., 2015, 2015, 829513.
[61]
Mousavi, S.H.; Moallem, S.A.; Mehri, S.; Shahsavand, S.; Nassirli, H.; Malaekeh-Nikouei, B. Improvement of cytotoxic and apoptogenic properties of crocin in cancre cell line by its nanoliposomal form. Pharm. Biol., 2011, 49, 1039-1045.
[62]
Mahdizadeh, S.; Karimi, G.; Behravan, J.; Arabzadeh, S.; Lage, H.; Kalalinia, F. Crocin suppresses multidrug resistence in MRP overexpressing ovarian cancer cell line. J. Pharm. Sci., 2016, 24, 17.
[63]
Xia, D. Ovarian cancer HO-8910 cell apoptosis induced by crocin in vitro. Nat. Prod. Commun., 2015, 10, 249-252.
[64]
Lu, P.; Lin, H.; Gu, Y.; Li, L.; Guo, H.; Wang, F.; Qiu, X. Antitumor effects of crocin on human breast cancer cells. Int. J. Clin. Exp. Med., 2015, 8, 20316-20322.
[65]
Mousavi, S.H.; Tavakkol-Afshari, J.; Brook, A.; Jafari-Anarkooli, I. Role of caspase and Bax protein in saffron-induced apoptosis in MCF-7 cells. Food Chem. Toxicol., 2009, 47, 1909-1913.
[66]
Chryssanthi, D.G.; Lamari, F.N.; Iatrou, G.; Pylara, A.; Karamanos, N.K.; Cordopatis, P. Inhibition of breast cancer cell proliferation by style constituents of different Crocus species. Anticancer Res., 2007, 27, 357-362.
[67]
Chyssanthi, D.G.; Dedes, P.G.; Karamanos, N.; Cordopatis, P.; Lamari, F. Crocetin inhibits invasiveness of MDA-MB-231 Breast cancer cells via downregulation of matrix metalloproteinases. Planta Med., 2011, 77, 146-1451.
[68]
Chryssanthi, D.G.; Lamari, F.; Gregoris, I.; Pylara, A.; Karamanos, N.K.; Cordopatis, P. Inhbition of breast cancer cells proliferation by style constituents of different crocus species. Anticancer Res., 2007, 27, 357-362.
[69]
Bakshi, H.A.; Hakkim, F.L.; Sam, S. Molecular mechanism of crocin induced caspase mediated MCF-7 cell death: In vivo toxicity profiling and ex vivo macrophage activation. Asian Pac. J. Cancer Prev., 2016, 17, 1499-1506.
[70]
Mostafavinia, S.E.; Khorashadizadeh, M.; Hoshyar, R. Antiprolifertaive and proapoptotic effects of crocin combined with hyperthermia on human breast cancer cells. DNA Cell Biol., 2016, 35, 340-347.
[71]
Vali, F.; Changizi, V.; Safa, M. Synergistic apoptotic effect of crocin and paclitaxel or crocin and radiation on MCF-7 cells, a type of breast cancer cell line. Int. J. Breast Cancer, 2015, 2015, 139349.
[72]
Ashrafi, M.; Bathaie, S.Z.; Abroun, S.; Azizian, M. Effect of crocin on cell cycle regulators in N. Nitroso-N-Methylurea-induced breast cancer in rats. DNA Cell Biol., 2015, 34, 684-691.
[73]
D’Alessandro, A.M.; Mancini, A.; Lizzi, A.R.; De-Simone, A.; Marroccella, C.E.; Gravina, G.L.; Tatone, C.; Festuccia, C. Crocus sativus stigma extract and its major constituent crocin possess significant antiproliferative properties against human prostate cancer. Nutr. Cancer, 2013, 65, 930-942.
[74]
Samarghandian, S.; Shabestari, M.M. DNA fragmentation and apoptosis induced by safranal in human prostate cancer cell line. Indian J. Urol., 2013, 29, 177-183.
[75]
Festuccia, C.; Mancini, A.; Gravina, G.L.; Scarsella, L.; Llorens, S.; Alonso, G.L.; Tatone, C.; Di-Cesare, E.; Jannini, E.A.; Lenzi, A.; D’Alessandro, A. Antitumor effects of saffron-derived carotenoids in prostate cancer cell models. BioMed Res. Int., 2014, 2014, 135048.
[76]
Morjani, H.; Tarantilis, P.; Polissiou, M.; Manfeit, M. Growth inhibition and induction of inhibition of erythroid differentation activity by crocin, dimethyl-crocetin and β-carotene on K562 cells. Anticancer Res., 1990, 10, 1398-1406.
[77]
Tarantilis, P.A.; Morjani, H.; Pollissiou, M.; Menfeit, M. Inhibition of growth and induction of differentiation of promyelocytic leukemia (HL-60) by carotenois from Crocus sativus L. Anticancer Res., 1994, 14, 1913-1918.
[78]
Nair, S.C.; Salomi, M.J.; Varghese, C.D.; Panikkar, B.; Panikkar, K.R. Effect of saffron on thymocyte proliferation, intracellular glutathione levels and its antitumor aciviy. Biofactors (Oxford, England),, 1992, 4, 51-54.
[79]
Xu, H.J.; Zhong, R.; Zhao, X.Y.; Li, X.R.; Lu, Y.; Song, A.Q.; Pang, X.Y.; Yao, R.Y.; Sun, L.R. Proliferative inhibition and apoptotic induction effects of crocin on human leukemia HL-60 cells anf their mechanism. Zhongguo Shi Xue Ye Xue Za Zhi, 2010, 18, 887-892.
[80]
Sun, Y.; Xu, H.J.; Zhao, Y.X.; Wang, L.Z.; Sun, L.R.; Wang, Z.; Sun, X.F. Crocin exhibits antitumor effects on human leukemia hl-60 cells in vitro and in vivo. Evid. Based Complement. Alternat. Med., 2013, 2013, 690164.
[81]
Rezaee, R.; Mahmoudi, M.; Abnous, K.; Zamani Taghizadeh Rabe, Z.T.S.; Tabasi, N.; Hashemzaei, M.; Karimi, G. Cytotoxic efects of crocin on MOLT-4 human laukemia cells. J. Complement. Integr. Med., 2013, 10(1), 105-112.
[82]
Sun, Y.; Wang, Z.; Wang, L.; Wang, L.Z.; Zang, C.; Sun, L.R. The effect and mechanism of proliferative inhibition of crocin on human leukaemia jurkat cells. West Indian Med. J., 2016, 64(5), 473.
[83]
García-Olmo, D.C.; Riese, H.H.; Escribano, J.; Ontañón, J.; Fernandez, J.A.; Atiénzar, M.; García-Olmo, D. Effects of long-term treatment of colon adenocarcinoma with crocin, a carotenoid from saffron (Crocus sativus L.): An experimental study in the rat. Nutr. Cancer, 1999, 35, 120-126.
[84]
Abdullaev, J.; Caballero-Ortega, H.; Riveròn-Negrete, L.; Pereda-Miranda, R.; Rivera-Luna, R.; Hernndez, M.J.; Perez-Lopez, I.; Espinosa-Aquirre, J.J. In vitro evaluation of the chemopreventive potential of saffron. Rev. Invest. Clin., 2002, 54, 430-436.
[85]
Bajbouj, K.; Schulze-Luehrmann, J.; Diemeier, S.; Amin, A.; Schneider-Stock, R. The anticancer effect of saffron in two p53 isogenic colorectal cancer cell lines. BMC Complement. Altern. Med., 2012, 28, 12-69.
[86]
Amin, A.; Bajbouij, K.; Koch, A.; Gandesiri, M.; Schneider-Stock, R. Defective autophagosome formation in p53-null colorectal cancer reinforces crocin-induced apoptosis. Int. J. Mol. Sci., 2015, 16, 1544-1561.
[87]
Ray, P.; Guha, D.; Chakraborty, J.; Banerjee, S.; Adhikary, A.; Chakraborty, S.; Das, T.; Sa, G. Crocetin exploits p53-Induced Death Domain (PIDD) and FAS-Associated Death Domain (FADD) proteins to induce apoptosis in colorectal cancer. Sci. Rep., 2016, 6, 32979.
[88]
Li, C.Y.; Huang, W.F.; Wang, Q.L.; Wang, F.; Cai, E.; Hu, B.; Du, J.C.; Wang, J.; Chen, R.; Cai, X.J.; Feng, J.; Li, H.H. Crocetin induces cytotoxicity in colon cancer cells via p53-independent mechanism. Asian Pac. J. Cancer Prev., 2012, 13, 3757-3761.
[89]
Aung, H.H.; Wang, C.Z.; Ni, M.; Fishbein, A.; Mehendale, S.R.; Xie, J.T.; Shoyama, C.Y.; Yuan, C.S. Crocin from Crocus Sativus posses significant antiproliferation effects on human colorectal cancer cells. Exp. Oncol., 2007, 29, 175-180.
[90]
Rastgoo, M.; Hosseinzadeh, H.; Alavizadeh, H.; Abbasi, A.; Ayati, Z.; Jaafari, M.R. Antitumor activity of PEGylated nanoliposome containing crocin in mice bearing C26 colon carcinoma. Planta Med., 2013, 79, 44-51.
[91]
Amin, A.; Hamza, A.A.; Daoud, S.; Khazanehdari, K.; Hrout, A.A.; Baig, B.; Chaiboonchoe, A.; Adrian, T.E.; Zaki, N.; Ashtiani, S.K. Saffron-based crocin prevents early lesions of liver cancer. In vivo, in vitro and network analyses. Rec. Pat. Anticancer Drug Discov., 2016, 11, 121-133.
[92]
Amin, A.; Hamza, A.A.; Bajouj, L.; Ashraf, S.S.; Daoud, S. Saffron: A potential candidate for a novel anticancer drug against hepatocellula carcinoma. Hepatology, 2011, 54, 857-867.
[93]
Lin, J.K.; Wang, C.J. Protection of crocin dyes on the acute hepatic damage induced by aflatoxin B1 and dimethylnitrosamine in rats. Carcinogenesis, 1986, 7, 595-599.
[94]
Wang, C.J.; Shiow, S.J.; Lin, J.K. Effects of crocetin on the hapatotoxicity and hepatic DNA binding of aflatoxin B1 in rats. Carcinogenesis, 1991, 12, 459-462.
[95]
Wang, C.J.; Shiah, H.S.; Lin, J.K. Modulatory effect of crocetin in aflatoxin B1 cytotoxicity and DNA adduct formation in C3H10t1/2 fibroblast cell. Cancer Lett., 1991, 56, 1-10.
[96]
Chang, W.C.; Lin, Y.L.; Lee, M.J.; Shiow, S.J.; Wang, C.J. Inhibitory effect of crocetin on benzo(a)pyrene genotoxicity and neoplastic transformation in C3H10T1/2 cells. Anticancer Res., 1996, 16, 3603-3608.
[97]
Tseng, T.H.; Chu, C.Y.; Huang, J.M.; Shiow, S.J.; Wang, C.J. Crocetin protects against oxidative damage in rat primary hepatocytes. Cancer Lett., 1995, 97, 61-67.
[98]
Escribano, J.; Alonso, G.L.; Coca-Prados, M.; Fernandez, A. Crocin saffranal and picocrocin from saffron (Crocus Sativus L.) inhibit the growth of human cancer cells in vitro. Cancer Lett., 1996, 100, 23-30.
[99]
Tavakkol-Afshari, J.; Brook, A.; Mousavi, S.H. Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines. Food Chem. Toxicol., 2008, 46, 3443-3447.
[100]
Amin, A.; Hamza, A.A.; Daoud, S.; Khazanehdari, K.; Hrout, A.A.; Baig, B.; Chaiboonchoe, A.; Adrian, T.E.; Zaki, N.; Salehi-Ashtiani, K. Saffron-based crocin prevents early lesions of liver cancer: In vivo, in vitro and network analyses. Rec. Pat. Anticancer Drug Discov., 2016, 11, 121-133.
[101]
Noureini, S.K.; Wink, M. Antiproliferative effects of crocin in HepG2 cells by telomerase inhibition and hTERT down-regulation. Asian Pac. J. Prev., 2012, 13, 2305-2309.
[102]
Dhar, A.; Mehta, S.; Dhar, G.; Dhar, K.; Banerjee, S.; Van Veldhuizen, P.; Campbell, D.R.; Banerjee, S.K. Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model. Mol. Cancer Ther., 2009, 8, 315-323.
[103]
Bakshi, H.; Sam, S.; Rozati, R.; Sultan, P.; Islam, T.; Rathore, B.; Lone, Z.; Sharma, M.; Triphati, J.; Saxena, R.C. DNA fragmentation and cell cycle arrest: A hallmark of apoptosis induced by crocin from kashmiri saffron in a human pancreatic cancer cell line. Asian Pac. J. Cancer Prev., 2010, 11, 675-679.
[104]
Rangarajan, P.; Subramaniam, D.; Paul, S.; Kwatra, D.; Palaniyandi, K.; Islam, S.; Harihar, S.; Ramalingam, S.; Gutheil, W.; Putty, S.; Pradhan, R.; Padhye, S.; Welch, D.R.; Anant, S.; Dhar, A. Crocetinic acid inhibits hedgehog signaling to inhibit pancreatic cancer stem cells. Oncotarget, 2015, 6, 27661-27673.
[105]
Terraf, P.; Kouhsari, S.M.; Ai, J.; Babaloo, H. Tissue-engineered regeneration of hemisected spinal cord using human endometrial stem cells, poly ε-caprolactone scaffolds, and crocin as a neuroprotective agent. Mol. Neurobiol., 2017, 54(7), 5657-5667.
[106]
Zhao, P.; Luo, C.L.; Wu, X.H.; Hu, H.B.; Lv, C.F.; Ji, H.Y. Proliferation apoptotic influence of crocin on human bladder T24 cell line. Zhongguo Zhongyao Zazhi, 2008, 33, 1869-1873.
[107]
Lv, C.F.; Luo, C.L.; Ji, H.Y.; Zhao, P. Influence of crocin on gene expression profile of human bladder cancer cell lines T24. Zhongguo Zhongyao Zazhi, 2008, 33, 1612-1617.
[108]
Samarghandian, S.; Boskabady, H.M.; Davoodi, S. Use of in vitro assays to assess the potential antiproliferative and cytotoxic effects of saffron (Crocus sativus L.) in human lung cancer cell line. Pharmacogn. Mag., 2010, 24, 309-314.
[109]
Samarghandian, S.; Borji, A.; Farahmand, K.; Afshari, R.; Davoodi, S. Crocus sativus L. (saffron) stigma aqueous extract induces apoptosis in alveolar human lung cancer cells through caspase-dependent pathways activation. BioMed Res. Int., 2013, 2013, 417928.
[110]
Magesh, V.; Singh, J.P.; Selvendiran, K.; Ekambaram, G.; Sakthisekaran, D. Antitumour activity of crocetin in accordance to tumor incidence, antioxidant status, drug metabolizing enzymes and histopathological studies. Mol. Cell. Biochem., 2006, 287, 127-135.
[111]
Magesh, V. DurgaBhavani, K.; Senthilnathan, P.; Rajendran, P.
Sakthisekaran, D. In vivo protective effect of crocetin on benzo(a)pyrene-induced lung cancer in Swiss albino mice. Phytother. Res., 2009, 23, 533-539.
[112]
Chen, S.; Zhao, S.; Wang, X.; Zhang, L.; Jiang, E.; Gu, Y.; Shanqquan, A.J.; Zhao, H.; Lv, T.; Yu, Z. Crocin inhibits cell proliferation and enhances cisplatin and pemetrexed chemosensitivity in lung cancer cells. Transl. Lung Cancer Res., 2015, 4, 775-783.
[113]
Li, X.; Huang, T.; Jiang, G.; Gong, W.; Qian, H.; Zou, C. Synergistic apoptotic effect of crocin and cisplatin on osteosarcoma cells via caspase induced apoptosis. Toxicol. Lett., 2013, 221, 197-204.
[114]
Bathaie, S.Z.; Miri, H.; Mohagheghi, M.A.; Mokhtari-Dizaji, M.; Shahbazfar, A.A.; Hasanzadeh, H. Saffron aqueous extract inhibits the chemically-induced gastric cancer progression in the wistar albino rat. Iran. J. Basic Med. Sci., 2013, 16, 27-38.
[115]
Hoshyar, R.; Bathaie, S.Z.; Sadeghizadeh, M. Crocin triggers the apoptotic through increasing the Bax/Bcl-2 ratio and caspase activation in human gastric adenocarcinoma, AGS, cells. DNA Cell Biol., 2013, 32, 50-57.
[116]
Luo, Y.; Cui, S.; Tang, F.; Shen, C.; Qi, Y.; Lu, D.; Ma, L.; Yang, Y.; Li, Y.; Chen, R.; Ri-Li, G.E. The combination of crocin with cisplatin suppresses growth of gastric carcinoma cell line BGC-823 and promotes cell apoptosis. Pak. J. Pharm. Sci., 2017, 30, 1629-1634.
[117]
Sun, J.; Xu, X.M.; Ni, C.Z.; Zhang, H.; Li, X.Y.; Zhang, C.L.; Liu, Y.R.; Li, S.F.; Zhou, Q.Z.; Zhou, H.M. Crocin inhibits proliferation and nucleic acid synthesis and induces apoptosis in the human tongue squamous cell carcinoma cell line Tca8113. Asian Pac. J. Cancer Prev., 2011, 12, 2679-2683.
[118]
Sheng, L.I.; Jiang, S.; Jiang, W.; Zhou, Y.; Shen, X-Y.; Luo, T.; Kong, L-P.; Wang, H-Q. Anticancer effects of crocetin in human esophageal squamous cell carcinoma KYSE-150 cells. Oncol. Lett., 2015, 9, 1254-1260.
[119]
Li, S.; Shen, X.Y.; Ouyang, T.; Qu, Y.; Luo, T.; Wang, H.Q. Synergistic anticancer effect of combined crocetin and cisplatin on KYSE-150 cells via p53/p21 pathway. Cancer Cell Int., 2017, 17, 98.
[120]
Esposito, E.; Drechsler, M.; Mariani, P.; Panico, A.M.; Cardile, V.; Crascì, L.; Carducci, F.; Graziano, A.C.; Cortesi, R.; Puglia, C. Nanostructured lipid dispersions for topical administration of crocin, a potent antioxidant from saffron (Crocus sativus L.). Mater. Sci. Eng. C Mater. Biol. Appl., 2017, 71, 669-677.
[121]
Rahaiee, S.; Hashemi, M.; Shojaosadati, S.A.; Moini, S.; Razavi, S.H. Nanoparticles based on crocin loaded chitosan-alginate biopolymers: Antioxidant activities, bioavailability and anticancer properties. Int. J. Biol. Macromol., 2017, 99, 401-408.
[122]
Rahaiee, S.; Shojaosadati, S.A.; Hashemi, M.; Moini, S.; Razavi, S.H. Improvement of crocin stability by biodegradeble nanoparticles of chitosan-alginate. Int. J. Biol. Macromol., 2015, 79, 423-432.
[123]
Mousavi, S.H.; Moallem, S.A.; Mehri, S.; Shahsavand, S.; Nassirli, H.; Malaekeh-Nikouei, B. Improvement of cytotoxic and apoptogenic properties of crocin in cancer cell lines by its nanoliposomal form. Pharm. Biol., 2011, 49, 1039-1045.
[124]
Malaekeh-Nikouei, B.; Mousavi, S.H.; Shahsavand, S.; Mehri, S.; Nassirli, H.; Moallem, S.A. Assessment of cytotoxic properties of safranal and nanoliposomal safranal in various cancer cell lines. Phytother. Res., 2013, 27, 1868-1873.
[125]
Mousavi, S.Z.; Amjad-Iranagh, S.; Nademi, Y.; Modarress, H. Carbon nanotube-encapsulated drug penetration through the cell membrane: An investigation based on steered molecular dynamics simulation. J. Membr. Biol., 2013, 246, 697-704.
[126]
El-Kharrag, R.; Amin, A.; Hisaindee, S.; Greish, Y.; Karam, S.M. Development of a therapeutic model of precancerous liver using crocin-coated magnetite nanoparticles. Int. J. Oncol., 2017, 50, 212-222.
[127]
Grumezescu, A.M.; Ghitulica, C.D.; Voicu, G.; Huang, K.S.; Yang, C.H.; Ficai, A.; Vasile, B.S.; Grumezescu, V.; Bleotu, C.; Chifiriuc, M.C. New silica nanostructure for the improved delivery of topical antibiotics used in the treatment of staphylococcal cutaneous infections. Int. J. Pharm., 2014, 463, 170-176.
[128]
Iliescu, R.I.; Andronescu, E.; Ghitulica, C.D.; Voicu, G.; Ficai, A.; Hoteteu, M. Montmorillonite-alginate nanocomposite as a drug delivery system--incorporation and in vitro release of irinotecan. Int. J. Pharm., 2014, 463, 184-192.
[129]
Vasile, B.S.; Oprea, O.; Voicu, G.; Ficai, A.; Andronescu, E.; Teodorescu, A.; Holban, A. Synthesis and characterization of a novel controlled release zinc oxide/gentamicin-chitosan composite with potential applications in wounds care. Int. J. Pharm., 2014, 463, 161-169.
[130]
Vlad, M.; Andronescu, E.; Grumezescu, A.M.; Ficai, A.; Voicu, G.; Bleotu, C.; Chifiriuc, M.C. Carboxymethyl-cellulose/Fe3O4 nanostructures for antimicrobial substances delivery. Biomed. Mater. Eng., 2014, 24, 1639-1646.
[131]
Andronescu, E.; Ficai, A.; Albu, M.G.; Mitran, V.; Sonmez, M.; Ficai, D.; Ion, R.; Cimpean, A. Collagen-hydroxyapatite/cisplatin drug delivery systems for locoregional treatment of bone cancer. Technol. Cancer Res. Treat., 2013, 12, 275-284.
[132]
Marques, C.; Ferreira, J.M.; Andronescu, E.; Ficai, D.; Sonmez, M.; Ficai, A. Multifunctional materials for bone cancer treatment. Int. J. Nanomedicine, 2014, 9, 2713-2725.
[133]
Wang, L.; Liu, S.; Zhang, X.; Xing, J.; Liu, Z.; Song, F. A strategy for identification and structural characterization of compounds from Gardenia jasminoides by integrating macroporous resin column chromatography and liquid chromatography-tandem mass spectrometry combined with ion-mobility spectrometry. J. Chromatogr. A, 2016, 1452, 47-57.
[134]
Zhou, W.E.; Zhang, Y.; Li, Y.; Ling, Y.; Li, H.N.; Li, S.H.; Jiang, S.J.; Ren, Z.Q.; Huang, Z.Q.; Zhang, F. Determination of gardenia yellow colorants in soft drink, pastry, instant noodles with ultrasound-assisted extraction by high performance liquid chromatography-electrospray ionization tandem mass spectrum. J. Chromatogr. A, 2016, 1446, 59-69.
[135]
Jadoon, S.; Karim, S.; Bin Asad, M.H.; Akram, M.R.; Khan, A.K.; Malik, A.; Chen, C.; Murtaza, G. Anti-aging potential of phytoextract loaded-pharmaceutical creams for human skin cell longetivity. Oxid. Med. Cell. Longev., 2015, 2015, 709628.
[136]
Gainer, J. Trans-sodium crocetinate for treating hypoxia/ischemia. Expert Opin. Investig. Drugs, 2008, 7, 917-924.
[137]
Gainer, J. New class of therapeutics that enhance small molecule diffusion. US patent 8,206,751, April 30 2009.
[138]
Gainer, J. Trans-sodium crocetinate, methods of making and methods of use thereof. US patent 6,060,511, May 9 2000.
[139]
Mohler, E.; Gainer, J.L.; Whitten, K.; Eraso, L.H.; Thanaporn, P.K.; Bauer, T. Evaluation of trans sodium crocetinate on safety and exercise performance in patients with peripheral artery disease and intermittent claudication. Vasc. Med., 2010, 16, 346-352.
[140]
Safety and efficacy study of trans sodium crocetinate (TSC) with concomitant radiation therapy and Temozolomide in newly diagnosed Glioblastoma (GBM). NCT01465347, 2011. ClinicalTrials. gov..

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy