Anti-cancer potential of Lactiplantibacillus plantarum NG28 through the induction of intrinsic apoptosis
Keywords:Probiotics, Lactiplantibacillus plantarum, colon cancer, HT-29, apoptosis
Introduction: Probiotics and fermented foods have become the focal point of research across different scientific disciplines, with recent findings indicating that Lactiplantibacillus plantarum (L. plantarum) isolated from various origins, holds significant promise in combating numerous diseases, including cancer. Hence, our current study seeks to explore how the L. plantarum NG28 strain might counteract the growth of HT-29 colorectal adenocarcinoma cells, potentially contributing to anti-cancer strategies.
Methods: The effect of the ethyl acetate extract of L. plantarum NG28 strain on HT-29 cells was evaluated in several ways. First, the cytotoxicity of HT-29 cells was determined by MTT assay. Additionally, the changes in cell morphology of HT-29 cells through DAPI staining and the induction of apoptosis using Annexin V-FITC/PI staining followed by flow cytometry were investigated. By using the RT-PCR and western blot techniques the expression of pro-apoptotic genes and proteins such as Bax, Caspase-9, and Caspase-3, as well as the anti-apoptotic gene Bcl-2 was examined.
Results: The findings revealed that the ethyl acetate extract of L. plantarum NG28 strain had a significant impact on the viability of HT-29 colon cancer cells in a dose-dependent manner, in contrast to its minimal effect on HUVEC cells. DAPI staining revealed the noticeable DNA damage and condensation of treated HT-29 cells and the flow cytometry strengthened the occurrence of apoptosis in the treated HT-29 cells. RT-PCR and western blot techniques investigated the intrinsic apoptosis of HT-29 cells through the increased expression levels of pro-apoptotic genes / proteins and decreased expression levels of anti-apoptotic gene.
Conclusion: The study demonstrated the anti-cancer activity of ethyl acetate extract of the L. plantarum NG28 strain against HT-29 colon cancer cells, primarily through the intrinsic apoptotic pathway. This suggests that L. plantarum NG28 strain could be used as a therapeutic tool in the inhibition and medication of colorectal cancer.
Badgeley, A., Anwar, H., Modi, K., Murphy, P., Lakshmikuttyamma, A. Effect of probiotics and gut microbiota on anti-cancer drugs: Mechanistic perspectives. BiochimBiophysActa Rev Cancer. 2020;1875(1):188494.
Yang, J., Wu, J., Li, Y., Zhang, Y., Cho, W.C., Ju,X,et. al., Gut bacteria formation and influencing factors. FEMS Microbiol Ecol. 2021;97(4): fiab043.
Su, Q., Liu, Q. Factors affecting gut microbiome in daily diet. Front Nutr. 2021;8:644138.
Hasan, N., Yang, H. Factors affecting the composition of the gut microbiota, and its modulation. PeerJ. 2019;7: e7502.
Jayakar, V., Lokapur, V., Nityasree, B.R., Chalannavar, R.K., Lasrado, L.D., Shantaram, M. Optimization and green synthesis of zinc oxide nanoparticle using Garcinia cambogia leaf and evaluation of their antioxidant and anticancer property in kidney cancer (A498) cell lines. Biomedicine. 2021 Jul 7;41(2):206-222.
Lokapur, V., Jayakar, V., Divakar, M.S., Chalannavar, R.K., Lasrado, L., Shantaram, M. ZnO nanoparticles with spectroscopically controlled morphology, bioinspired from Holigarna grahamii (Wight) Kurz and delving its antioxidant and anticancer potential on A498 cell line. Materials Today Communications. 2022 Jun 1;31:103338.
Labianca, R., Beretta, G.D., Kildani, B., Milesi, L., Merlin, F., Mosconi, S., et. al., Colon cancer. Crit Rev OncolHematol. 2010;74(2):106-133.
Elfahri, K.R., Vasiljevic, T., Yeager, T., Donkor, O.N. Anti-colon cancer and antioxidant activities of bovine skim milk fermented by selected Lactobacillus helveticus strains. J Dairy Sci. 2016;99(1):31-40.
Azizi, N.F., Kumar, M.R., Yeap, S.K., Abdullah, J.O., Khalid, M., Omar,.AR., et. al.,Kefir and its biological activities. Foods. 2021;10(6):1210.
Williams, N.T. Probiotics. Am J Health Syst Pharm.2010;67(6):449-458.
Sherman, P.M., Ossa, J.C., Johnson-Henry, K. Unraveling mechanisms of action of probiotics. NutrClinPract. 2009;24(1):10-14.
Piqué, N., Berlanga, M., Miñana-Galbis, D. Health Benefits of Heat-Killed (Tyndallized) Probiotics: An overview. Int J Mol Sci. 2019;20(10):2534.
Sharifi, M., Moridnia, A., Mortazavi, D., Salehi, M., Bagheri, M., Sheikhi, A. Kefir: a powerful probiotic with anticancer properties. Med Oncol. 2017;34(11):183.
Kassayova M, Bobrov N, Strojny L, Orendas P, Demeckova V, Jendzelovsky R, Kubatka P, Kiskova T, Kruzliak P, Adamkov M, Bomba A, Fedorocko P. Anticancer and Immunomodulatory Effects of Lactobacillus plantarum LS/07, Inulin and melatonin in NMU-induced rat model of breast cancer. Anticancer Res. 2016;36(6):2719-2728.
Chuah, L.O., Foo, H.L., Loh, T.C., Mohammed,Alitheen, N.B., Yeap.S.K.,et. al., Postbiotic metabolites produced by Lactobacillus plantarum strains exert selective cytotoxicity effects on cancer cells. BMC Complement Altern Med. 2019;19(1):114.
Shankar, S., Jayarama. S., Gopal, S. Assessment of antioxidant and anti-inflammatory activities of probiotic Lactiplantibacillusplantarum strains isolated from traditional fermented food products Ngari and Soibum. Asian J. Pharmaceutics. 2023;17(3): 01-11
Amin, M., Navidifar, T., Saeb, S., Barzegari, E., Jamalan,M.Tumor-targeted induction of intrinsic apoptosis in colon cancer cells by Lactobacillus plantarum and Lactobacillus rhamnosus strains. MolBiol Rep. 2023;50(6):5345-5354.
Khan, I., Kang, S.C. Apoptotic activity of Lactobacillus plantarum DGK 17 fermented soybean seed extract in human colon cancer cells via ROS-JNK Signaling Pathway. J Food Sci. 2017;82(6):1475-1483.
Maleki-Kakelar, H., Dehghani, J., Barzegari, A., Barar, J., Shirmohamadi, M., Sadeghi, J., Omidi, Y. Lactobacillus plantarum induces apoptosis in gastric cancer cells via modulation of signaling pathways in Helicobacter pylori. Bioimpacts. 2020;10(2):65-72.
Hwang, C.H., Lee, N.K., Paik. H.D. The anti-cancer potential of heat-killed Lactobacillus brevis KU15176 upon AGS cell lines through intrinsic apoptosis pathway. Int J Mol Sci. 2022;23(8):4073.
Faghfoori, Z., Faghfoori, M.H., Saber, A., Izadi, A., YariKhosroushahi, A. Anticancer effects of bifidobacteria on colon cancer cell lines. Cancer Cell Int. 2021;21(1):258.
Srinivas, B.K., Shivamadhu. M.C., Jayarama, S. Musa acuminata lectin exerts anti-cancer effects on HeLa and EAC cells via activation of caspase and inhibitions of Akt, Erk, and Jnk pathway expression and suppresses the neoangiogenesis in in-vivo models. Int J BiolMacromol. 2021;166:1173-1187.
Park, J., Kwon, M., Lee, J., Park, S., Seo, J., Roh, S. Anti-cancer effects of Lactobacillus plantarum L-14 cell-free extract on human malignant melanoma A375 cells. Molecules. 2020;25(17):3895.
Jeong, S., Kim, Y., Park, S., Lee, D., Lee, J., Hlaing, S.P., et. al., Lactobacillus plantarum metabolites elicit anticancer effects by inhibiting autophagy-related responses. Molecules. 2023;28(4):1890.
Wei, Y., Li, F., Li, L., Huang, L., Li, Q. Genetic and biochemical characterization of an exopolysaccharide with in vitro antitumoral activity produced by Lactobacillus fermentum YL-11. Front Microbiol. 2019; 10:2898.
Nami, Y., Abdullah, N., Haghshenas, B., Radiah, D., Rosli, R., Khosroushahi, A.Y. Assessment of probiotic potential and anticancer activity of newly isolated vaginal bacterium Lactobacillus plantarum 5BL. Microbiol. Immunol. 2014;58(9):492-502.
Pourramezan, Z., Oloomi, M., Kasra-Kermanshahi, R. Antioxidant and anticancer activities of Lactobacillus hilgardii strain AG12a. Int J Prev Med. 2020;11:132.
Lee, J.E., Lee, J., Kim, J.H., Cho, N., Lee, S.H., Park, S.B., et. al., Characterization of the anti-cancer activity of the probiotic bacterium Lactobacillus fermentum using 2D vs. 3D culture in colorectal cancer cells. Biomolecules. 2019;9(10):557.
Russo, F., Orlando, A., Linsalata, M., Cavallini, A., Messa, C. Effects of Lactobacillus rhamnosus GG on the cell growth and polyamine metabolism in HGC-27 human gastric cancer cells. Nutr Cancer. 2007;59(1):106-114.
How to Cite
Copyright (c) 2023 Biomedicine
This work is licensed under a Creative Commons Attribution 4.0 International License.