Impact of Taurine on the Proliferation and Apoptosis of Human Cervical Carcinoma Cells and Its Mechanism
Cervical cancer is one of the most significant health challenges faced by women globally, ranking fourth in both incidence and mortality rates among all cancers. It poses a severe threat to physical and mental health, necessitating the development of effective treatments. This study explores the role of Taurine (Tau) in inhibiting the proliferation and inducing apoptosis in human cervical carcinoma cells, specifically the SiHa cell line, and investigates the underlying mechanisms involving the mammalian sterile 20-like kinase 1 (MST1) pathway.
Introduction
Cervical cancer is a major malignant tumor in the female reproductive system, with human papillomavirus (HPV) infection being the primary trigger. Over 90% of cervical cancer cases are associated with HPV, particularly through the E6 and E7 oncogenes. These genes disrupt normal cellular functions by targeting tumor suppressor proteins such as p53 and retinoblastoma (Rb). Despite advancements in surgery and chemoradiotherapy, treatment options for advanced or metastatic cervical cancer remain limited, highlighting the need for novel therapeutic approaches. Molecular targeted therapies, including those involving Tau, offer promising avenues for treatment.
Tau, chemically known as 2-aminoethanesulfonic acid, is an abundant amino acid in the human body with diverse biological functions, including regulating osmotic pressure, calcium balance, and exhibiting anti-oxidative and anti-inflammatory effects. Previous studies have shown that Tau can synergize with chemotherapeutic agents like cisplatin, enhancing their efficacy while reducing toxicity. However, the detailed mechanisms of Tau’s anti-cancer effects remain unclear. This study aims to elucidate the role of Tau in cervical cancer cell apoptosis and its interaction with the MST1 pathway.
Methods
The study utilized the human cervical cancer cell line SiHa, which was transfected with the recombinant plasmid pEGFP-N1-MST1 to overexpress MST1. Cell proliferation was assessed using the MTT assay, apoptosis was measured via flow cytometry, and protein expression levels were analyzed using Western blotting. The effects of Tau on cell proliferation and apoptosis were evaluated at various concentrations (10, 20, 40, 80, 160, and 320 mmol/L) over different time periods (24, 48, and 72 hours). The overexpression of MST1 was confirmed, and its impact on Tau-induced apoptosis was examined.
Results
Inhibition of Cell Proliferation by Tau
Tau significantly inhibited the proliferation of SiHa cells in a dose- and time-dependent manner. The IC50 values for Tau at 24, 48, and 72 hours were 239.87 mmol/L, 113.05 mmol/L, and 92.62 mmol/L, respectively. These results indicate that Tau has a potent inhibitory effect on cervical cancer cell proliferation.
Induction of Apoptosis by Tau
Tau induced apoptosis in SiHa cells, with apoptotic rates of 21.95% and 30% at concentrations of 160 mmol/L and 320 mmol/L, respectively. These rates were significantly higher than those in the control group. The pro-apoptotic effects of Tau were comparable to those of cisplatin, a clinically used chemotherapeutic agent.
Regulation of Apoptosis-Related Proteins by Tau
Tau upregulated the expression of pro-apoptotic proteins MST1 and Bax while downregulating the anti-apoptotic protein Bcl-2. The expression levels of MST1 and Bax increased with higher Tau concentrations, whereas Bcl-2 expression decreased. These changes were statistically significant, indicating that Tau promotes apoptosis through the regulation of these proteins.
Enhancement of Apoptosis by MST1 Overexpression
Overexpression of MST1 enhanced the pro-apoptotic effects of Tau. The apoptotic rates in the Tau group, p-EGFP-MST1 group, and p-EGFP-MST1+Tau group were 20.52%, 33.19%, and 64.1%, respectively. These results suggest that MST1 plays a crucial role in Tau-induced apoptosis.
Regulation of Apoptosis-Related Genes by MST1 Overexpression
MST1 overexpression upregulated the mRNA expression of pro-apoptotic genes p73, p53, PUMA, and caspase-3 while downregulating the expression of CTGF, AREG, and YAP. The protein levels of p73, p53, PUMA, and caspase-3 were also increased, and the phosphorylation of YAP was enhanced. These findings indicate that MST1 promotes apoptosis through multiple signaling pathways.
Discussion
The study demonstrates that Tau inhibits the proliferation and induces apoptosis in cervical cancer SiHa cells. The upregulation of MST1 and Bax, along with the downregulation of Bcl-2, suggests that Tau promotes apoptosis through the mitochondrial pathway. Additionally, MST1 overexpression enhances Tau’s pro-apoptotic effects, indicating a synergistic relationship between Tau and MST1.
The MST1-Hippo signaling pathway plays a critical role in regulating cell proliferation and apoptosis. MST1 overexpression leads to the upregulation of pro-apoptotic proteins and the downregulation of cell proliferation-related genes, further supporting its role in Tau-induced apoptosis. The interaction between the Hippo pathway and other signaling pathways, such as the p53 pathway, highlights the complexity of Tau’s anti-cancer mechanisms.
The findings of this study provide valuable insights into the potential use of Tau as a therapeutic agent for cervical cancer. By targeting the MST1 pathway, Tau offers a novel approach to inducing apoptosis in cancer cells, particularly in cases where traditional treatments are ineffective. Future research should focus on elucidating the detailed mechanisms of Tau’s action and exploring its efficacy in clinical settings.
Conclusion
Tau inhibits the proliferation and induces apoptosis in cervical cancer SiHa cells through the upregulation of MST1 and Bax and the downregulation of Bcl-2. MST1 plays a pivotal role in enhancing Tau’s pro-apoptotic effects, making it a potential target for cervical cancer therapy. The study underscores the importance of molecular targeted therapies in the treatment of cervical cancer and highlights the need for further research to optimize Tau’s therapeutic potential.
doi.org/10.1097/CM9.0000000000000162
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