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Anti-Cancer Agents in Medicinal Chemistry


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

Research Article

Correlation between Antioxidant/Antimutagenic and Antiproliferative Activity of Some Phytochemicals

Author(s): Doaa T. Ramadan, Mohamed A.M. Ali, Shaymaa M. Yahya and Wael M. El-Sayed*

Volume 19 , Issue 12 , 2019

Page: [1481 - 1490] Pages: 10

DOI: 10.2174/1871520619666190528091648

Price: $65


Background: Chemotherapeutic drugs have high toxicity associated with undesirable side-effects. Now, natural products are the most important anti-cancer agents because of their low toxicity and potential effectiveness.

Methods: The half maximal inhibitory concentration (IC50) of amygdalin, naringenin and ellagic acid against breast, colon, and liver cell lines was estimated. The antimutagenic, free radical-, superoxide radical-, and hydroxyl radical- scavenging activities of these phytochemicals were measured. The expression of p53, bid, bax, bcl2, and caspases 9, 3, and 7 was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in breast and liver cells. In addition, the active Caspase 3 protein was estimated in liver cells.

Results: Ellagic acid showed the highest antioxidant and antiproliferative activities. Amygdalin and naringenin with low and moderate antioxidant profiles showed a corresponding low and moderate cytotoxicity against cancer cell lines, respectively. Naringenin and ellagic acid had a significant antimutagenic activity which was detected by the Salmonella test. Ellagic acid offered a much better antimutagenic activity than naringenin. The apoptotic pathway evoked by ellagic acid in HepG2 and MCF-7 cells was investigated. The results showed that a caspase-dependent and a caspase-independent apoptosis occurred in MCF-7 and HepG2, respectively.

Conclusion: The antimutagenic/antioxidant properties are well correlated with the antiproliferative activity of the phytochemicals investigated. This study proved that some easy, quick and cheap assays could predict the antiproliferative activity of many nutraceuticals. Finally, this platform could help in the discovery of new anticancer agents where hundreds of compounds are investigated in the pipeline of drug discovery.

Keywords: Amygdalin, naringenin, ellagic acid, antioxidant activity, antimutagenicity, phytochemicals.

Graphical Abstract
Jemal, A.; Bray, F.; Center, M.M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. Cancer J. Clin., 2011, 61, 69-90.
Pratheeshkumar, P.; Sreekala, C.; Zhang, Z.; Budhraja, A.; Ding, S.; Son, K.; Wang, X.; Hitron, A.; Hyun-Jung, K.; Wang, L.; Lee, J.; Shi, X. Cancer prevention with promising natural products: Mechanisms of action and molecular targets. Anti-Cancer Ag. Med. Chem., 2012, 12, 1-26.
Todorova, A.; Pesheva, M.; Iliev, I.; Bardarov, K.; Todorova, T. Antimutagenic, antirecombinogenic, and antitumor effect of amygdalin in a yeast cell-based test and mammalian cell lines. J. Med. Food, 2017, 20(4), 360-366.
Sumathi, R.; Tamizharasi, S.; Sivakumar, T. Bio-dynamic activity of naringenin - A review. Int. J. Curr. Adv. Res., 2015, 4(8), 234-236.
Pitchakarn, P.; Chewonarin, T.; Ogawa, K.; Suzuki, S.; Asamoto, M.; Takahashi, S.; Shirai, T.; Limtrakul, P. Ellagic acid inhibits migration and invasion by prostate cancer cell lines. Asian Pac. J. Cancer Prev., 2013, 14(5), 2859-2863.
Sepúlveda, L.; Ascacio, A.; Rodríguez-Herrera, R.; Aguilera-Carbó, A.; Aguilar, C.N. Ellagic acid: Biological properties and biotechnological development for production processes. Afr. J. Biotechnol., 2011, 10(22), 4518-4523.
El-Sayed, W.M.; Hussin, W.A.; Mahmoud, A.A.; AlFredan, M.A. (). The Conyza triloba extracts with high chlorophyll content and free radical scavenging activity had anticancer activity in cell lines. BioMed Res. Int., 2013, 2013, 1-11.
Udhayasankar, M.R.; Danya, U.; Punitha, D.; Arumugasamy, K. (). Antioxidant activity of Cardiospermum canescens wall. (sapindaceae)- A wild edible plant from Western Ghats. Int. J. Pharm. Pharm. Sci., 2013, 5(2), 322-324.
Repetto, G.; Peso, A.; Zurita, J.L. Neutral red uptake assay for the estimation of cell viability/cytotoxicity. Nat. Protoc., 2008, 3(7), 1125-1131.
El-Sayed, W.M.; Hussin, W.A. Antimutagenic and antioxidant activity of novel 4-substituted phenyl-2,2′-bichalcophenes and aza-analogs. Drug Des. Devel. Ther., 2013, 7, 73-81.
El-Sayed, W.M.; Hussin, W.A.; Franklin, M.R. The antimutagenicity of 2-substituted selenazolidine-4-(R)-carboxylic acids. Mutat. Res., 2007, 627(2), 136-145.
Hong, C.E.; Cho, M.C.; Jang, H.A.; Lyu, S.Y. Mutagenicity and anti-mutagenicity of Acanthopanax divaricatus var. albeofructus. J. Toxicol. Sci., 2011, 36(5), 661-668.
Rao, X.; Huang, X.; Zhou, Z.; Lin, X. An improvement of the 2^(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis. Biostat. Bioinforma. Biomath., 2013, 3(3), 71-85.
Brewer, M.S. Natural antioxidants: Sources, compounds, mechanisms of action, and potential applications. Compr. Rev. Food Sci. Food Saf., 2011, 10, 221-247.
Heim, K.E.; Tagliaferro, A.R.; Bobilya, D.J. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J. Nutr. Biochem., 2002, 13, 572-584.
Park, H.J.; Yoon, S.H.; Han, L.S.; Zheng, L.T.; Jung, K.H.; Uhm, Y.K.; Lee, J.H.; Jeong, J.S.; Joo, W.S.; Yim, S.V.; Chung, J.H.; Hong, S.P. Amygdalin inhibits genes related to cell cycle in SNU-C4 human colon cancer cells. World J. Gastroenterol., 2005, 11(33), 5156-5161.
Krishnakumar, N.; Sulfikkarali, N. RajendraPrasad, N.; Karthikeyan, S. Enhanced anticancer activity of naringenin-loaded nanoparticles in human cervical (HeLa) cancer cells. Biomed. Preventive Nutrit., 2011, 1, 223-231.
Kocyigit, A.; Koyuncu, I.; Dikilitas, M.; Bahadori, F.; Turkkan, B. Cytotoxic, genotoxic and apoptotic effects of naringenin-oxime relative to naringenin on normal and cancer cell lines. Asian Pac. J. Trop. Biomed., 2016, 6(10), 872-880.
a)Araújo, J.R.; Gonçalves, P.; Martel, F. Chemopreventive effect of dietary polyphenols in colorectal cancer cell lines. Nutr. Res., 2011, 31, 77-87.
b)Vukovic, N.L.; Obradovic, A.D.; Vukic, M.D.; Jovanovic, D.; Djurdjevic, P.M. Cytotoxic, proapoptotic and antioxidative potential of flavonoids isolated from propolis against colon (HCT-116) and breast (MDAMB-231) cancer cell lines. Food Res. Int., 2017, 106, 71-80.
Kuo, M.; Lee, K.; Lin, J. Genotoxicities of nitropyrenes and their modulation by apigenin, tannic acid, ellagic acid and indole-3-carbinol in the Salmonella and CHO systems. Mutat. Res., 1992, 270, 87-95.
Mortelmans, K.; Zeiger, E. The Ames Salmonella microsome mutagenicity assay. Mutat. Res., 2000, 455, 29-60.
Kaur, S.J.; Grover, I.S.; Kumar, S. (). Modulatory effects of a tannin fraction isolated from Terminalia arjuna on the genotoxicity of mutagens in Salmonella typhimurium. Food Chem. Toxicol., 2000, 38, 1113-1119.
Fulda, S.; Debatin, K.M. Caspase Activation in Cancer Therapy.,
Lawen, A. Apoptosis—An introduction. BioEssays, 2003, 25, 888-896.
Shabalala, S.; Louw, J.; Muller, C.; Johnson, R. Polyphenols, autophagy and doxorubicin-induced cardiotoxicity. Life Sci., 2017, 180, 160-170.

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