EFFECT OF ZINC PYRITHIONE ON INFLAMMATION-INDUCED EPITHELIAL-MESENCHYMAL TRANSITION IN COLORECTAL CANCER CELL LINES

V. Brahmaiah, G. Deepthi Reddy, B. Y. Kavitha and G. Deepika*

ABSTRACT

Background: Colorectal cancer is a major global health concern, with metastasis significantly contributing to patient mortality. Inflammation within the tumor microenvironment plays a critical role in promoting CRC progression, notably by inducing the epithelial-mesenchymal transition. EMT is a process where epithelial cells lose their characteristic cell-cell adhesion and gain migratory and invasive properties, facilitating metastasis. Zinc Pyrithione, a coordination complex based on zinc, has demonstrated antimicrobial and anti-proliferative effects. The study revealed that Zinc Pyrithione efficiently reduces epithelial-mesenchymal transition in colorectal cancer cell lines HT-29 and SW480 in the context of inflammation and TGF-β stimulation. Methods: Colorectal cancer cell lines SW480 and HT-29 were exposed to inflammatory conditions to induce EMT. Subsequently, the cells were treated with varying concentrations of ZnPT. The expression of epithelial and mesenchymal markers, specifically E-cadherin, N-cadherin, Vimentin, and Snail, was then assessed using Western blot analysis to determine the impact of ZnPT on these key EMT markers. Results: ZnPT treatment effectively attenuated inflammation-induced EMT in both SW480 and HT-29 cells. This attenuation was characterized by a reversal of the inflammation-induced changes in EMT marker expression. ZnPT treatment led to an increase in the levels of the epithelial marker E-cadherin, which is typically downregulated during EMT, and a concomitant decrease in the levels of mesenchymal markers N-cadherin, Vimentin, and Snail, which are typically upregulated during EMT. Conclusion: ZnPT demonstrates a significant ability to suppress inflammation-induced EMT in CRC cell lines by modulating the expression of key EMT markers. These findings suggest that ZnPT holds promise as a therapeutic agent for preventing CRC metastasis by targeting inflammation-driven EMT processes. Further studies are needed to elucidate the precise mechanisms of action and to evaluate the in vivo efficacy of ZnPT in CRC models. Zinc is an essential trace element, playing important roles in cellular processes. Disruptions in zinc levels can have deleterious effects on cell.

Keywords: Zinc Pyrithione, Colorectal Cancer, Epithelial-Mesenchymal Transition, Metastasis, LPS, TGF-?, Inflammation.