INTERNATIONAL CONGRESS OF
CancerGenetics
The Role of Probiotics in Inducing Apoptosis and Regulating Apoptosis-Related Gene Expression in Gastrointestinal Cancer Therapy
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Mahdieh Abbasi,1,* javad allahverdi,2
1. Iran university of medical sience
2. Iran university of medical sience
- Introduction: Apoptosis, or programmed cell death, is a crucial mechanism that maintains cellular homeostasis by eliminating damaged or abnormal cells (1). In cancer, particularly gastrointestinal cancers, the disruption of apoptotic pathways allows cancer cells to evade death, leading to uncontrolled proliferation (2). Recent studies suggest that probiotics, such as Lactobacillus and Bifidobacterium species, can trigger apoptosis in cancer cells by modulating various molecular and genetic pathways (3). This article reviews the potential of probiotics to induce apoptosis in cancer cells and their effects on the expression of apoptosis-related genes.
- Methods: The study is based on a comprehensive review of research focused on the interaction between probiotics and apoptosis in gastrointestinal cancer cells. Specifically, studies analyzing the effects of probiotics on key apoptotic markers such as p53, Bax, Bcl-2, and caspase activity were included. Data on the molecular pathways involved in apoptosis induction, such as the mitochondrial and death receptor pathways, were also considered.
- Results: 1. Activation of the Mitochondrial Apoptosis Pathway: Probiotics have been shown to induce apoptosis via the intrinsic mitochondrial pathway. For example, Lactobacillus acidophilus enhances the expression of pro-apoptotic proteins such as Bax while reducing anti-apoptotic proteins like Bcl-2 , leading to mitochondrial membrane permeabilization and the release of cytochrome c. This release triggers the activation of caspases, particularly caspase-9 and caspase-3, culminating in cancer cell apoptosis (4, 5). 2. Influence on the Death Receptor Pathway: The death receptor pathway is another key apoptotic route that probiotics can modulate. Studies show that Bifidobacterium longum can upregulate death receptors like Fas and TRAIL on the surface of cancer cells, making them more susceptible to apoptosis. This effect promotes the activation of caspase-8, further enhancing the apoptotic cascade (6). 3. Regulation of Tumor Suppressor Genes: Probiotics are known to regulate crucial tumor suppressor genes involved in apoptosis. For example, Lactobacillus casei has been shown to increase the expression of p53, a tumor suppressor that plays a central role in promoting apoptosis in response to DNA damage. Through this mechanism, probiotics can restore the apoptotic response in cancer cells where p53 activity is otherwise diminished (7). 4. Downregulation of Anti-Apoptotic Genes: In cancer, many cells overexpress anti-apoptotic genes, allowing them to evade apoptosis. Probiotics such as Lactobacillus rhamnosus GG have been reported to downregulate anti-apoptotic genes like Bcl-2 and Bcl-xL, which are commonly overexpressed in gastrointestinal cancer cells. This reduction in anti-apoptotic signals facilitates the initiation of the apoptotic process, leading to cancer cell death (8). 5. Caspase Activation and Apoptotic Cascade: Caspases are essential executors of apoptosis, and probiotics have been shown to activate caspase enzymes directly. Research indicates that Bifidobacterium bifidum can trigger the activation of both initiator caspases (such as caspase-8 and caspase-9) and executioner caspases (caspase-3), leading to efficient and irreversible apoptosis in cancer cells (9). This suggests that probiotics may serve as a natural trigger for the caspase-dependent apoptotic pathway in gastrointestinal cancers.
- Conclusion: Probiotics have demonstrated significant potential in inducing apoptosis in gastrointestinal cancer cells by regulating various apoptotic pathways and gene expressions. By targeting the mitochondrial and death receptor pathways, probiotics can influence key regulators such as p53, Bax, Bcl-2, and caspases, effectively promoting programmed cell death in cancerous tissues. The ability of probiotics to modulate these molecular mechanisms positions them as promising adjunctive agents in cancer therapy. Future studies should focus on clinical trials to better understand the full therapeutic potential of probiotics in inducing apoptosis and inhibiting cancer progression. 1. Kari S, Subramanian K, Altomonte IA, Murugesan A, Yli-Harja O, Kandhavelu M. Programmed cell death detection methods: a systematic review and a categorical comparison. Apoptosis. 2022;27(7):482-508. 2. Wang H, Liu M, Zeng X, Zheng Y, Wang Y, Zhou Y. Cell death affecting the progression of gastric cancer. Cell death discovery. 2022;8(1):377. 3. Nowak A, Paliwoda A, Błasiak J. Anti-proliferative, pro-apoptotic and anti-oxidative activity of Lactobacillus and Bifidobacterium strains: A review of mechanisms and therapeutic perspectives. Critical reviews in food science and nutrition. 2019;59(21):3456-67. 4. Taheri F, Moazamian E, Mahdavi M. Lactobacillus acidophilus Cytotoxicity Effect and Apoptosis in Human Bladder Carcinoma Cells: An In Vitro Study. Immunoregulation. 2020;3(2):127-34. 5. Yue Y, Wang S, Shi J, Xie Q, Li N, Guan J, et al. Effects of Lactobacillus acidophilus KLDS1. 0901 on proliferation and apoptosis of colon cancer cells. Frontiers in Microbiology. 2022;12:788040. 6. Faghfoori Z, Faghfoori MH, Saber A, Izadi A, Yari Khosroushahi A. Anticancer effects of bifidobacteria on colon cancer cell lines. Cancer cell international. 2021;21(1):258. 7. Dadfarma N, Nowroozi J, Kazemi B, Bandehpour M. Identification of the effects of acid-resistant Lactobacillus casei metallopeptidase gene under colon-specific promoter on the colorectal and breast cancer cell lines. Iranian Journal of Basic Medical Sciences. 2021;24(4):506. 8. 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. Molecular Biology Reports. 2023;50(6):5345-54. 9. Kim S-J, Kang C-H, Kim G-H, Cho H. Anti-tumor effects of heat-killed L. reuteri MG5346 and L. casei MG4584 against human colorectal carcinoma through caspase-9-dependent apoptosis in xenograft model. Microorganisms. 2022;10(3):533.
- Keywords: Probiotics, apoptosis, Gastrointestinal Cancer, p53
