In vitro cytotoxic activity of probiotic bacterial cell extracts against Caco-2 and HRT-18 colorectal cancer cells
Keywords:probiotic, colorectal cancer, lactic acid bacteria, Lactobacilus, MTT, cytotoxicity
This research aimed at screening the anti-cancer activity of cell extracts of forty potential probiotic bacterial isolates against 2 colorectal cancer (CRC) cell lines (namely, Caco-2 and HRT-18), and vero cells using 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) and Trypan Blue assays (TBE). Results demonstrated that 2 isolates (Lactobacillus acidophilus LA102 and Lactobacillus casei LC232) showed pronounced cytotoxic activities, with proliferation inhibition of 37% and 68.5% of LA102, and 48% and 45.7% of LC232 against Caco-2 and HRT-18, respectively, at a concentration of 100 μg extract/ml. The IC50 values of the cytotoxic activity were 1.6 and 2.5 μg/ml of LA102, and 15.4 and 6.2 μg/ml of LC232 against Caco-2 and HRT-18, respectively. At the same time, results showed that LA102 and LC232 isolates had no cytotoxic effect on the normal vero cells. Even though these observations raise the prospects of using these probiotic isolates for possible cancer prevention and even treatment, yet further investigation is needed to ascertain their potential to prevent in vivo human CRC.
Altonsy MO, Andrews SC, Tuohy KM. Differential induction of apoptosis in human colonic carcinoma cells (Caco-2) by Atopobium, and commensal, probiotic and enteropathogenic bacteria: Mediation by the mitochondrial pathway. Int J Food Mic. 2010; 137: 190–203.
Assaf MA, Haddadin RN, Aldouri NA, Alabbassi R, Mashallah S, Mohammad M, Bustanji Y. Anti-cancer, anti-inflammatory and anti-microbial activities of plant extracts used against hematological tumors in traditional medicine of Jordan. Journal of Ethnopharmacology. 2013; 145(3):728-736.
Awaisheh SS, Ibrahim SA. Screening of antibacterial activity of lactic acid bacteria against different pathogens found in vacuum packaged meat products. Foodborne Pathogens and Disease. 2009; 6(9):115-123.
Awaisheh SS. Probiotic food products classes, types, and processing. In: Everlon CR. (ed.) Probiotics. Intech Publisher, Croatia. 2012. P. 551-582.
Awaisheh SS. Development of probiotic soft cheese manufactured using goat’s milk with the addition of thyme. Milchwissenschaft. 2011; 66:51–54.
Boik J. Natural compounds in cancer therapy. Oregon. Medical Press, Minnesota, USA, 2001.
Choi SS, Kim Y, Han KS, You KS, You S, Oh S, Kim SH. Effects of Lactobacillus strains on cancer cell proliferation and oxidative stress in vitro. Letters in Applied Microbiology. 2006; 42:452–458.
Daniluk U. Probiotics, the New Approach for Cancer Prevention and/or Potentialization of Anti-Cancer Treatment. Journal of Clinical & Experimental Oncology. 2012; 1(2):1-2.
Fichera GA, Giese G. Non-immunologically-mediated cytotoxicity of Lactobacillus casei and its derivative peptidoglycan against tumor cell lines. Cancer Letters. 1994; 85: 93–103.
Haroun BM, Refaat BM, El- Menoufy HA, Amin HA, El-Waseif AA. Structure Analysis and Antitumor Activity of the Exopolysaccharide from Probiotic Lactobacillus plantarum NRRL B- 4496 In vitro
and In vivo. Journal of Applied Sciences Research. 2013; 9(1):425-434.
Hassan M, Watari H, AbuAlmaaty A, Ohba Y, Sakuragi N. Apoptosis and molecular targeting therapy in cancer, BioMed Research International. 2014; 1:1-23.
Hyun JY, Deok-Kun O, Geun EJ. Anticancerogenic effect of a novel chiroinositol-containing polysaccharide from Bifidobacterium bifidum BGN4. FEMS Microbiology Letters. 2004; 240:131–136.
Kim JY, Woo HJ, Kim YS, Kim KH, Lee HJ. Cell cycle dysregulation induced by cytoplasm of Lactococcus lactis ssp. lactis in SNUC2A, a colon cancer cell line. Nutrition and Cancer. 2003; 46:197–201.
Lau CB, Ho CY, Kim CF, Leung KN, Fung KP, Tse TF, Chan HH. Cytotoxic activities of Coriolus versicolor (Yunzhi) extract on human leukemia and lymphoma cells by induction of apoptosis. Life Sciences. 2004; 7:797–798.
Le LRK, Hu Y, Brown IL, Woodman RJ, Young GP. Synbiotic intervention of Bifidobacterium lactis and resistant starch protects against colorectal cancer development in rats. Carcinogenes. 2010; 31:246-251.
Lee JW, Shin JG, Kim EH, Kang HE, Yim IB, Kim JY, Joo HG, Woo HJ. Immunomodulatory and antitumor effects in vivo by the cytoplasmic fraction of Lactobacillus casei and Bifidobacterium longum. Journal of Veterinary Science. 2004; 5:41–48.
Manjunath N, Ranganathan B. A cytotoxic substance produced by a wild culture of Lactobacillus casei D-34 against tumour cells. Indian journal of experimental of Biology. 1989; 27:141–145.
Nowak A, Libudzisz Z. Ability of probiotic Lactobacillus casei DN 114001 to bind or/and metabolise heterocyclic aromatic amines in vitro. European Journal of Nutrition. 2009; 48:419-427.
Oda M, Hasegawa H, Komatsu S, Kambe M, Tsuchiya F. Anti-tumor polysaccharide from Lactobacillus sp.. Agriculture and Biological Chemistry. 1983; 47:1623–1625.
Perdigón G, Fuller R, Raya R. Lactic acid bacteria and their effect on the immune system. Current Issues in Intestinal Microbiology. 2011; 2:27-42.
Phonnok S, Wanlaya U, Tanechpongtamb B, Thanomsub W. Anticancer and apoptosis-inducing activities of microbial metabolites. Electronic Journal of Biotechnology. 2010; 13(5):1-12.
Rafter J. Probiotics and colon cancer. Best Practice & Research of Clinical Gastroenterology. 2003; 17(5):849–859.
Rebecca S, Jiemin M, Zhaohui Z, Ahmadin J.Cancer Statistic. CA Cancer Journal Clinic. 2014; 64:9-29.
Roberfroid M. Prebiotics: the concept revisited The Journal of Nutrition. 2007; 137:830S-837S.
Rowland IR, Rumney CJ, Coutts JT, Lievense LC. Effect of Bifidobacterium longum and inulin on gut bacterial metabolism and carcinogen-induced aberrant crypt foci in rats. Carcinogenes. 1998; 19:281-285.
Roy M-J, Dionne S, Marx G, Qureshi I, Sarma D, Levy E, Seidman EG. In vitro studies on the inhibition of colon cancer by butyrate and carnitine. Nutrition. 2009; 25:1193–1201.
Sevda ER, Ayşe TK, Merih K. Cytotoxic effects of various lactic acid bacteria on Caco-2 cells. Turkish Journal of Biology. 2015; 39:23-30.
Takagi A, Matsuzaki T, Sato M, Nomoto K, Morotomi M, Yokokura T. Enhancement of natural killer cytotoxicity delayed murine carcinogenesis by a probiotic microorganism. Carcinogenesis. 2001; 22:599-605.
Zhong L, Zhang X, Covasa M. Emerging roles of lactic acid bacteria in protection against colorectal cancer. World Journal of Gastroenterology. 2014; 28(24):7878-7886.