Inhibitory effects of probiotic Bacillus coagulans against MCF7 breast cancer cells
,
Abstract
Background and Objectives: Secondary metabolites in the supernatants of probiotic microorganisms have shown anticancer effects. The present study was aimed to investigate the cytotoxicity of Bacillus coagulans supernatants and their role in apoptosis induction in MCF7 cancer cells.
Materials and Methods: The inhibition of MCF7 cancer cells by Bacillus coagulans supernatants was assessed by MTT assay at three exposure times of 24, 48, and 72 h. Apoptosis induction was explored by flow cytometry while the expression levels of bax, caspase 3, caspase 9, and bcl2 were examined by real-time PCR and compared with normal HFF cells.
Results: Bacillus coagulans supernatants exhibited inhibitory effects on MCF7 cells in a concentration-dependent and time-dependent manner; while lower cytotoxic effects were observed in normal HFF cells. The increase in the expression of bax, caspase 3, and caspase 9 genes and the decrease in the anti-apoptotic gene of bcl2, along with the flow cytometry results, confirmed the induction of apoptosis in the cancer cells.
Conclusion: Regarding the cytotoxic influence of Bacillus coagulans supernatants against breast cancer cells, this bacterium can be considered as a potential candidate for a novel therapeutic strategy with lower side effects which of course requires further investigations.
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6. Lopes CM, Dourado A, Oliveira R. Phytotherapy and nutritional supplements on breast cancer. Biomed Res Int 2017;2017:7207983.
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9. Al-Oqail MM, Al-Sheddi ES, Farshori NN, Al-Massarani SM, Al-Turki EA, Ahmad J, et al. Corn silk (Zea mays L.) induced apoptosis in human breast cancer (MCF-7) cells via the ROS-mediated mitochondrial pathway. Oxid Med Cell Longev 2019;2019:9789241.
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11. Reid G. The growth potential for dairy probiotics. Int Dairy J 2015;49:16-22.
12. Georgiev K, Georgieva M, Iliev I, Peneva M, Alexandrov G. Antiproliferative effect of Bulgarian spring water probiotics (Lakter a Nature Probiotics®), against human colon carcinoma cell line. World J Pharm Pharm Sci 2015;4:130-136.
13. Zhou J, Ouyang J, Xu Q, Zheng Z. Cost-effective simultaneous saccharification and fermentation of l-lactic acid from bagasse sulfite pulp by Bacillus coagulans CC17. Bioresour Technol 2016;222:431-438.
14. Adams CA. The probiotic paradox: live and dead cells are biological response modifiers. Nutr Res Rev 2010;23:37-46.
15. Mojibi P, Tafvizi F, Bikhof Torbati M. Cell-bound exopolysaccharide extract from indigenous probiotic bacteria induce apoptosis in HT-29 cell-line. Iran J Pathol 2019;14:41-51.
16. Khodaii Z, Ghaderian SMH, Natanzi MM. Probiotic bacteria and their supernatants protect enterocyte cell lines from enteroinvasive Escherichia coli (EIEC) invasion. Int J Mol Cell Med 2017;6:183-189.
17. Wang K, Li W, Rui X, Chen X, Jiang M, Dong M. Characterization of a novel exopolysaccharide with antitumor activity from Lactobacillus plantarum 70810. Int J Biol Macromol 2014;63:133-139.
18. Nozari S, Faridvand Y, Etesami A, Ahmad Khan Beiki M, Miresmaeili Mazrakhondi SA, Abdolalizadeh J. Potential anticancer effects of cell wall protein fractions from Lactobacillus paracasei on human intestinal Caco-2 cell line. Lett Appl Microbiol 2019;69:148-154.
19. Karimi Ardestani S, Tafvizi F, Tajabadi Ebrahimi M. Heat-killed probiotic bacteria induce apoptosis of HT-29 human colon adenocarcinoma cell line via the regulation of Bax/Bcl2 and caspases pathway. Hum Exp Toxicol 2019;38:1069-1081.
20. Hassan Z, Mustafa S, Rahim RA, Isa NM. Anti-breast cancer effects of live, heat-killed and cytoplasmic fractions of Enterococcus faecalis and Staphylococcus hominis isolated from human breast milk. In vitro Cell Dev Biol Anim 2016;52:337-348.
21. Tiptiri-Kourpeti A, Spyridopoulou K, Santarmaki V, Aindelis G, Tompoulidou E, Lamprianidou EE, et al. Lactobacillus casei exerts anti-proliferative effects accompanied by apoptotic cell death and up-regulation of TRAIL in colon carcinoma cells. PLoS One 2016;11(2):e0147960.
22. Chobdar N, Ahmadizadeh C. The effect of Lactobacillus brevis on apoptosis and casp (casp8, casp3) gene expression in HeLa cancer cells. Iran J Med Microbiol 2020;14:84-100.
23. LeBlanc H, Lawrence D, Varfolomeev E, Totpal K, Morlan J, Schow P, et al. Tumor-cell resistance to death receptor--induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. Nat Med 2002;8:274-281.
24. Konuray G, Erginkaya Z. Potential use of Bacillus coagulans in the food industry. Foods 2018;7:92.
25. Adibpour N, Hosseininezhad M, Pahlevanlo A, Hussain MA. A review on Bacillus coagulans as a spore-forming probiotic. Appl Food Biotechnol 2019;6:91-100.
26. Kawarizadeh A, Nojoomi F, Tabatabaei M, Hosseinzadeh S, Farzaneh M. The effect of Bacillus coagulans on cytotoxicity and apoptosis induced by Salmonella Typhimurium in HT-29 cell culture. Iran J Microbiol 2019;11:305-312.
27. Lee JE, Lee J, Kim JH, Cho N, Lee SH, Park SB, 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;9:557.
28. Riaz Rajoka MS, Zhao H, Lu Y, Lian Z, Li N, Hussain N, et al. Anticancer potential against cervix cancer (HeLa) cell line of probiotic Lactobacillus casei and Lactobacillus paracasei strains isolated from human breast milk. Food Funct 2018;9:2705-2715.
29. Nouri Z, Karami F, Neyazi N, Modarressi MH, Karimi R, Khorramizadeh MR, et al. Dual anti-metastatic and anti-proliferative activity assessment of two probiotics on HeLa and HT-29 cell lines. Cell J 2016;18:127-134.
30. Nami Y, Abdullah N, Haghshenas B, Radiah D, Rosli R, Khosroushahi AY. Assessment of probiotic potential and anticancer activity of newly isolated vaginal bacterium Lactobacillus plantarum 5BL. Microbiol Immunol 2014;58:492-502.
31. Nami Y, Abdullah N, Haghshenas B, Radiah D, Rosli R, Khosroushahi AY. Probiotic potential and biotherapeutic effects of newly isolated vaginal Lactobacillus acidophilus 36YL strain on cancer cells. Anaerobe 2014;28:29-36.
32. Saberian M, Shahidi Delshad E, Habibi M. The Effect of Bifidobacterium bifidum supernatant and cell mass on the proliferation potential of rat bone marrow-derived stromal cells. Iran J Med Sci 2020;45:269-276.
33. Dehghani N, Tafvizi F, Jafari P. Cell cycle arrest and anti-cancer potential of probiotic Lactobacillus rhamnosus against HT-29 cancer cells. Bioimpacts 2021;11:245-252.
34. Elfahri KR, Vasiljevic T, Yeager T, Donkor ON. Anti-colon cancer and antioxidant activities of bovine skim milk fermented by selected Lactobacillus helveticus strains. J Dairy Sci 2016;99:31-40.
35. Malik SS, Saeed A, Baig M, Asif N, Masood N, Yasmin A. Anticarcinogenecity of microbiota and probiotics in breast cancer. Int J Food Prop 2018;21:655-666.
36. Ahmadi MA, Ebrahimi MT, Mehrabian S, Tafvizi F, Bahrami H, Dameshghian M. Antimutagenic and anticancer effects of lactic acid bacteria isolated from Tarhana through Ames test and phylogenetic analysis by 16S rDNA. Nutr Cancer 2014;66:1406-1413.
37. Asadollahi P, Ghanavati R, Rohani M, Razavi S, Esghaei M, Talebi M. Anti-cancer effects of Bifidobacterium species in colon cancer cells and a mouse model of carcinogenesis. PLoS One 2020;15(5):e0232930.
38. Sehrawat N, Yadav M, Singh M, Kumar V, Sharma VR, Sharma AK. Probiotics in microbiome ecological balance providing a therapeutic window against cancer. Semin Cancer Biol 2021;70:24-36.
39. Nami Y, Haghshenas B, Haghshenas M, Abdullah N, Yari Khosroushahi A. The prophylactic effect of probiotic Enterococcus lactis IW5 against different human cancer cells. Front Microbiol 2015;6:1317.
40. Madempudi RS, Kalle AM. Antiproliferative effects of Bacillus coagulans unique IS2 in colon cancer cells. Nutr Cancer 2017;69:1062-1068.
41. Lee NK, Son SH, Jeon EB, Jung GH, Lee JY, Paik HD. The prophylactic effect of probiotic Bacillus polyfermenticus KU3 against cancer cells. J Funct Foods 2015;14:513-518.
2. Roshandel G, Ghanbari-Motlagh A, Partovipour E, Salavati F, Hasanpour-Heidari S, Mohammadi G, et al. Cancer incidence in Iran in 2014: results of the Iranian national population-based cancer registry. Cancer Epidemiol 2019;61:50-58.
3. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-249.
4. Wu D, Si M, Xue HY, Wong HL. Nanomedicine applications in the treatment of breast cancer: current state of the art. Int J Nanomedicine 2017;12:5879-5892.
5. Roshandel G, Semnani S, Fazel A, Honarvar M, Taziki M, Sedaghat S, et al. Building cancer registries in a lower resource setting: the 10-year experience of Golestan, northern Iran. Cancer Epidemiol 2018;52:128-133.
6. Lopes CM, Dourado A, Oliveira R. Phytotherapy and nutritional supplements on breast cancer. Biomed Res Int 2017;2017:7207983.
7. Hassan Z. Anti-cancer and biotherapeutic potentials of probiotic bacteria. J Cancer Sci Ther 2019;11:9-13.
8. Górska A, Przystupski D, Niemczura MJ, Kulbacka J. Probiotic bacteria: A promising tool in cancer prevention and therapy. Curr Microbiol 2019;76:939-949.
9. Al-Oqail MM, Al-Sheddi ES, Farshori NN, Al-Massarani SM, Al-Turki EA, Ahmad J, et al. Corn silk (Zea mays L.) induced apoptosis in human breast cancer (MCF-7) cells via the ROS-mediated mitochondrial pathway. Oxid Med Cell Longev 2019;2019:9789241.
10. Jafari-Nasab T, Khaleghi M, Farsinejad A, Khorrami S. Probiotic potential and anticancer properties of Pediococcus sp. isolated from traditional dairy products. Biotechnol Rep (Amst) 2021;29:e00593.
11. Reid G. The growth potential for dairy probiotics. Int Dairy J 2015;49:16-22.
12. Georgiev K, Georgieva M, Iliev I, Peneva M, Alexandrov G. Antiproliferative effect of Bulgarian spring water probiotics (Lakter a Nature Probiotics®), against human colon carcinoma cell line. World J Pharm Pharm Sci 2015;4:130-136.
13. Zhou J, Ouyang J, Xu Q, Zheng Z. Cost-effective simultaneous saccharification and fermentation of l-lactic acid from bagasse sulfite pulp by Bacillus coagulans CC17. Bioresour Technol 2016;222:431-438.
14. Adams CA. The probiotic paradox: live and dead cells are biological response modifiers. Nutr Res Rev 2010;23:37-46.
15. Mojibi P, Tafvizi F, Bikhof Torbati M. Cell-bound exopolysaccharide extract from indigenous probiotic bacteria induce apoptosis in HT-29 cell-line. Iran J Pathol 2019;14:41-51.
16. Khodaii Z, Ghaderian SMH, Natanzi MM. Probiotic bacteria and their supernatants protect enterocyte cell lines from enteroinvasive Escherichia coli (EIEC) invasion. Int J Mol Cell Med 2017;6:183-189.
17. Wang K, Li W, Rui X, Chen X, Jiang M, Dong M. Characterization of a novel exopolysaccharide with antitumor activity from Lactobacillus plantarum 70810. Int J Biol Macromol 2014;63:133-139.
18. Nozari S, Faridvand Y, Etesami A, Ahmad Khan Beiki M, Miresmaeili Mazrakhondi SA, Abdolalizadeh J. Potential anticancer effects of cell wall protein fractions from Lactobacillus paracasei on human intestinal Caco-2 cell line. Lett Appl Microbiol 2019;69:148-154.
19. Karimi Ardestani S, Tafvizi F, Tajabadi Ebrahimi M. Heat-killed probiotic bacteria induce apoptosis of HT-29 human colon adenocarcinoma cell line via the regulation of Bax/Bcl2 and caspases pathway. Hum Exp Toxicol 2019;38:1069-1081.
20. Hassan Z, Mustafa S, Rahim RA, Isa NM. Anti-breast cancer effects of live, heat-killed and cytoplasmic fractions of Enterococcus faecalis and Staphylococcus hominis isolated from human breast milk. In vitro Cell Dev Biol Anim 2016;52:337-348.
21. Tiptiri-Kourpeti A, Spyridopoulou K, Santarmaki V, Aindelis G, Tompoulidou E, Lamprianidou EE, et al. Lactobacillus casei exerts anti-proliferative effects accompanied by apoptotic cell death and up-regulation of TRAIL in colon carcinoma cells. PLoS One 2016;11(2):e0147960.
22. Chobdar N, Ahmadizadeh C. The effect of Lactobacillus brevis on apoptosis and casp (casp8, casp3) gene expression in HeLa cancer cells. Iran J Med Microbiol 2020;14:84-100.
23. LeBlanc H, Lawrence D, Varfolomeev E, Totpal K, Morlan J, Schow P, et al. Tumor-cell resistance to death receptor--induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. Nat Med 2002;8:274-281.
24. Konuray G, Erginkaya Z. Potential use of Bacillus coagulans in the food industry. Foods 2018;7:92.
25. Adibpour N, Hosseininezhad M, Pahlevanlo A, Hussain MA. A review on Bacillus coagulans as a spore-forming probiotic. Appl Food Biotechnol 2019;6:91-100.
26. Kawarizadeh A, Nojoomi F, Tabatabaei M, Hosseinzadeh S, Farzaneh M. The effect of Bacillus coagulans on cytotoxicity and apoptosis induced by Salmonella Typhimurium in HT-29 cell culture. Iran J Microbiol 2019;11:305-312.
27. Lee JE, Lee J, Kim JH, Cho N, Lee SH, Park SB, 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;9:557.
28. Riaz Rajoka MS, Zhao H, Lu Y, Lian Z, Li N, Hussain N, et al. Anticancer potential against cervix cancer (HeLa) cell line of probiotic Lactobacillus casei and Lactobacillus paracasei strains isolated from human breast milk. Food Funct 2018;9:2705-2715.
29. Nouri Z, Karami F, Neyazi N, Modarressi MH, Karimi R, Khorramizadeh MR, et al. Dual anti-metastatic and anti-proliferative activity assessment of two probiotics on HeLa and HT-29 cell lines. Cell J 2016;18:127-134.
30. Nami Y, Abdullah N, Haghshenas B, Radiah D, Rosli R, Khosroushahi AY. Assessment of probiotic potential and anticancer activity of newly isolated vaginal bacterium Lactobacillus plantarum 5BL. Microbiol Immunol 2014;58:492-502.
31. Nami Y, Abdullah N, Haghshenas B, Radiah D, Rosli R, Khosroushahi AY. Probiotic potential and biotherapeutic effects of newly isolated vaginal Lactobacillus acidophilus 36YL strain on cancer cells. Anaerobe 2014;28:29-36.
32. Saberian M, Shahidi Delshad E, Habibi M. The Effect of Bifidobacterium bifidum supernatant and cell mass on the proliferation potential of rat bone marrow-derived stromal cells. Iran J Med Sci 2020;45:269-276.
33. Dehghani N, Tafvizi F, Jafari P. Cell cycle arrest and anti-cancer potential of probiotic Lactobacillus rhamnosus against HT-29 cancer cells. Bioimpacts 2021;11:245-252.
34. Elfahri KR, Vasiljevic T, Yeager T, Donkor ON. Anti-colon cancer and antioxidant activities of bovine skim milk fermented by selected Lactobacillus helveticus strains. J Dairy Sci 2016;99:31-40.
35. Malik SS, Saeed A, Baig M, Asif N, Masood N, Yasmin A. Anticarcinogenecity of microbiota and probiotics in breast cancer. Int J Food Prop 2018;21:655-666.
36. Ahmadi MA, Ebrahimi MT, Mehrabian S, Tafvizi F, Bahrami H, Dameshghian M. Antimutagenic and anticancer effects of lactic acid bacteria isolated from Tarhana through Ames test and phylogenetic analysis by 16S rDNA. Nutr Cancer 2014;66:1406-1413.
37. Asadollahi P, Ghanavati R, Rohani M, Razavi S, Esghaei M, Talebi M. Anti-cancer effects of Bifidobacterium species in colon cancer cells and a mouse model of carcinogenesis. PLoS One 2020;15(5):e0232930.
38. Sehrawat N, Yadav M, Singh M, Kumar V, Sharma VR, Sharma AK. Probiotics in microbiome ecological balance providing a therapeutic window against cancer. Semin Cancer Biol 2021;70:24-36.
39. Nami Y, Haghshenas B, Haghshenas M, Abdullah N, Yari Khosroushahi A. The prophylactic effect of probiotic Enterococcus lactis IW5 against different human cancer cells. Front Microbiol 2015;6:1317.
40. Madempudi RS, Kalle AM. Antiproliferative effects of Bacillus coagulans unique IS2 in colon cancer cells. Nutr Cancer 2017;69:1062-1068.
41. Lee NK, Son SH, Jeon EB, Jung GH, Lee JY, Paik HD. The prophylactic effect of probiotic Bacillus polyfermenticus KU3 against cancer cells. J Funct Foods 2015;14:513-518.
| Files | ||
| Issue | Vol 13 No 6 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v13i6.8089 | |
| Keywords | ||
| Apoptosis; Bacillus coagulans; Breast cancer; Probiotic; Supernatant | ||
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How to Cite
1.
Dolati M, Tafvizi F, Salehipour M, Komeili Movahed T, Jafari P. Inhibitory effects of probiotic Bacillus coagulans against MCF7 breast cancer cells. Iran J Microbiol. 2021;13(6):839-847.
