Protective role of Lactobacillus plantarum A7 against irinotecan-induced genotoxicity

Document Type : Original Research Article


1 Department of Pharmacology, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

2 Food Security Research Centre, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

3 Department of Pharmacodynamy and Toxicology, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.


Objective: Irinotecan is a botanical derivative and an anti-cancer drug with cytotoxic and genotoxic effects. The present study evaluated the effect of Lactobacillus plantarum A7 on the genotoxic activity of irinotecan in a hepatocellular carcinoma cell line (HepG2) by comet assay.
Materials and Methods: HepG2 were incubated with irinotecan (100 µM), heat-killed cells (0.025 µg/ml) + irinotecan (100 µM), and cell-free supernatants (0.5 and 1 µg/ml) of L. plantarum A7 + irinotecan (100 µM). Phosphate buffered saline (PBS) was used as negative control.
Results: Irinotecan was shown to induce DNA damage in HepG2 cells. The results showed that heat-killed cells (0.025 µg/ml) and cell-free supernatants (0.5 and 1 µg/ml) of L. plantarum significantly reduce irinotecan- induced DNA damage.
Conclusion: Our results indicate that L. plantarum A7 can decrease the genotoxic effects of irinotecan in HepG2 cells, in vitro. This finding may be supportive for the optimization of therapeutic efficacy in irinotecan treatment.


Main Subjects

Apás AL, González SN, Arena ME. 2014. Potential of goat probiotic to bind mutagens. Anaerobe, 28: 8-12
Burns AJ, Rowland IR. 2004. Antigenotoxicity of probiotics and prebiotics on faecal water-induced DNA damage in human colon adenocarcinoma cells. Mutat Res, 551: 233-43.
Cai Z, Yang J, Shu X and Xiong X. 2014. Chemotherapy-associated hepatotoxicity in colorectal cancer. Vascular, 14: 15.
Caldini G, Trotta F, Villarini M, Moretti M, Pasquini R,  Scassellati-Sforzolini G, Cenci G. 2005. Screening of potential lactobacilli antigenotoxicity by microbial and mammalian cell-based tests. Int J Food Microbiol, 102: 37-47.
Chávez-Tapia NC, González-Rodríguez m L, Jeong M, López-Ramírez Y, Barbero-Becerra V, Juárez-Hernández E, Romero-Flores J. L, Arrese M, Méndez-Sánchez N and Uribe M. 2015. Current evidence on the use of probiotics in liver diseases. J Funct Foods, 17:137-151.
Cragg GM, Newman DJ. 2005. Plants as a source of anti-cancer agents. J Ethnopharmacol, 100: 72-79.
Etebari M, Ghannadi A, Jafarian-Dehkordi A, Ahmadi F. 2012. Genotoxicity evaluation of aqueous extracts of co-toneaster discolor and Alhagi pseudalhagi by com-et assay. J Res Med Sci, 17:S237–S241.
Fazeli H, Moshtaghian J, Mirlohi M, Shirzad M. 2010. Reduction in serum lipid parameters by incorporation of a native strain of Lactobacillus Plantarum A7 in Mice. J Diabetes Metab Disord, 9: 1-7.
Jafarian A, Zolfaghari B, Shirani K. 2014. Cytotoxicity of different extracts of arial parts of Ziziphus spina-christi on Hela and MDA-MB-468 tumor cells. Adv Biomed Res, 3: 38.
Kahouli I, Tomaro-Duchesneau C, Prakash S. 2013. Probiotics in colorectal cancer (CRC) with emphasis on mechanisms of action and current perspectives. J Med Microbiol, 62: 1107-23.
Kontek R, Drozda R, Śliwiński M, Grzegorczyk K. 2010. Genotoxicity of irinotecan and its modulation by vitamins A, C and E in human lymphocytes from healthy individuals and cancer patients. Toxicol In Vitro, 24: 417-24.
Kumar K, Sastry N, Polaki H, Mishra V. 2015. Colon Cancer Prevention through Probiotics: An Overview. J Cancer Sci Ther, 7: 081-92.
Lévesque É, Bélanger A-S, Harvey M,Couture   F, Jonker D, Innocenti F, Cecchin E, Toffoli G and Guillemette C. 2013. Refining the UGT1A haplotype associated with irinotecan-induced hematological toxicity in metastatic colorectal cancer patients treated with 5-fluorouracil/irinotecan-based regimens. J Pharmacol Exp Ther, 345: 95-101.
Parvez S, Malik K, Ah Kang S, Kim HY. 2006. Probiotics and their fermented food products are beneficial for health. J Appl Microbiol, 100: 1171-85.
Pool‐Zobel BL, Münzner R, Holzapfel WH. 1993. Antigenotoxic properties of lactic acid bacteria in the S. typhimurium mutagenicity assay. Nutr Cancer, 20: 261–270.
Raman M, Ambalam P, Kondepudi KK, Pithva S, Kothari C, Patel AT, Purama RK, Dave JM, Vyas BR. 2013. Potential of probiotics, prebiotics and synbiotics for management of colorectal cancer. Gut microbes, 4: 181-92.
Razavi-Azarkhiavi K, Behravan J, Mosaffa F, Sehatbakhsh S, Shirani K, Karimi G. 2014. Protective effects of aqueous and ethanol extracts of rosemary on H2O2-induced oxidative DNA damage in human lymphocytes by comet assay. J Complement Integr Med, 11: 27-33.
Sadeghi-Aliabadi H, Mohammadi F, Fazeli H, Mirlohi M. 2014. Effects of Lactobacillus plantarum A7 with probiotic potential on colon cancer and normal cells proliferation in comparison with a commercial strain. Iran J Basic Med Sci, 17: 815–819.
Santos A, Zanetta S, Cresteil T, Deroussent A, Pein F, Raymond E, Vernillet L, Risse ML, Boige V, Gouyette A, Vassal G. 2000. Metabolism of irinotecan (CPT-11) by CYP3A4 and CYP3A5 in humans. Clin Cancer Res, 6: 2012-20.
Vajro P, Mandato C, Licenziati MR, Franzese A, Vitale DF, Lenta S, Caropreso M, Vallone G, Meli R. 2011. 2011. Effects of Lactobacillus rhamnosus strain GG in pediatric obesityrelated liver disease. J Pediatr Gastroenterol Nutr, 52: 740–743.