EGFR gene regulation in colorectal cancer cells by garlic phytocompounds with special emphasis on S-Allyl-L-Cysteine Sulfoxide
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Colorectal cancer is one among the most common cancers in the world and a major cause of cancer related deaths. Similar to other cancers, colorectal carcinogenesis is often associated with over expression of genes related to cell growth and proliferation, especially Epidermal Growth Factor Receptor (EGFR). There is an increasing attention towards the plant derived compounds in prevention of colorectal carcinogenesis by downregulating EGFR. Among plants, garlic (Allium sativum L.) is emerging with anticancer properties by virtue of its organosulfur compounds. The present study was aimed to analyze the interaction ability of garlic compounds in the active region of EGFR gene by in silico molecular docking studies and in vitro validation. This was conducted using the Discovery studio software version 4.0. Among the tested compounds, s-allyl-l-cysteine-sulfoxide (SACS)/alliin showed higher affinity towards EGFR. Furthermore, wet lab analysis using cell viability test and EGFR expression analysis in colorectal cancer cells confirmed its efficacy as a potent anticancer agent.
KeywordsColorectal cancer Allium sativum EGFR S-allyl-L-cysteine-sulfoxide Molecular docking Discovery studio
Nabarun Roy acknowledges the financial support by the Department of Biotechnology, Ministry of Science and Technology, Govt. of India, through its HRD programme (BT/DI/03/014/2002). Arunaksharan Narayanankutty is thankful to the Council of Scientific and Industrial Research for Senior Research Fellowship (09/869 (0012)/2012-EMR-I).
Compliance with ethical standards
Conflict of interest
The authors declare to have no conflict of interest in the present study.
- 5.Duffy MJ, Lamerz R, Haglund C, Nicolini A, Kalousova M, Holubec L, Sturgeon C (2014) Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update. Int J Cancer 134(11):2513–2522. doi: 10.1002/ijc.28384 CrossRefPubMedGoogle Scholar
- 19.Barlow DJ, Buriani A, Ehrman T, Bosisio E, Eberini I, Hylands PJ (2012) In silico studies in Chinese herbal medicines’ research: evaluation of in-silico methodologies and phytochemical data sources, and a review of research to date. J Ethnopharmacol 140(3):526–534. doi: 10.1016/j.jep.2012.01.041 CrossRefPubMedGoogle Scholar
- 21.Rose PW, Prlic A, Bi C, Bluhm WF, Christie CH, Dutta S, Green RK, Goodsell DS, Westbrook JD, Woo J, Young J, Zardecki C, Berman HM, Bourne PE, Burley SK (2015) The RCSB protein data bank: views of structural biology for basic and applied research and education. Nucleic Acids Res 43(Database issue):345–356. doi: 10.1093/nar/gku1214 CrossRefGoogle Scholar
- 23.Vanommeslaeghe K, Hatcher E, Acharya C, Kundu S, Zhong S, Shim J, Darian E, Guvench O, Lopes P, Vorobyov I, Mackerell AD Jr (2010) CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J Comput Chem 31(4):671–690. doi: 10.1002/jcc.21367 CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Yoshikawa S, Kukimoto-Niino M, Parker L, Handa N, Terada T, Fujimoto T, Terazawa Y, Wakiyama M, Sato M, Sano S, Kobayashi T, Tanaka T, Chen L, Liu ZJ, Wang BC, Shirouzu M, Kawa S, Semba K, Yamamoto T, Yokoyama S (2013) Structural basis for the altered drug sensitivities of non-small cell lung cancer-associated mutants of human epidermal growth factor receptor. Oncogene 32(1):27–38. doi: 10.1038/onc.2012.21 CrossRefPubMedGoogle Scholar
- 34.Arunkumar R, Sharmila G, Elumalai P, Senthilkumar K, Banudevi S, Gunadharini DN, Benson CS, Daisy P, Arunakaran J (2012) Effect of diallyl disulfide on insulin-like growth factor signaling molecules involved in cell survival and proliferation of human prostate cancer cells in vitro and in silico approach through docking analysis. Phytomedicine 19(10):912–923. doi: 10.1016/j.phymed.2012.04.009 CrossRefPubMedGoogle Scholar
- 56.Wang K, Wang Y, Qi Q, Zhang F, Zhang Y, Zhu X, Liu G, Luan Y, Zhao Z, Cai J, Cao J, Li S (2016) Inhibitory effects of S-allylmercaptocysteine against benzo(a)pyrene-induced precancerous carcinogenesis in human lung cells. Int Immunopharmacol 34:37–43. doi: 10.1016/j.intimp.2016.02.017 CrossRefPubMedGoogle Scholar
- 60.Chen Y, Henson ES, Xiao W, Huang D, McMillan-Ward EM, Israels SJ, Gibson SB (2016) Tyrosine kinase receptor EGFR regulates the switch in cancer cells between cell survival and cell death induced by autophagy in hypoxia. Autophagy 12(6):1029–1046. doi: 10.1080/15548627.2016.1164357 CrossRefPubMedPubMedCentralGoogle Scholar