EGCG inhibits tobacco smoke-promoted proliferation of lung cancer cells through targeting CCL5

Background

The occurrence and development of cancer are deeply intertwined with chronic inflammatory processes. Epigallocatechin gallate (EGCG), the most pharmacologically potent catechin derived from tea, has garnered attention for its anti-inflammatory and anti-carcinogenic properties. However, the molecular mechanisms through which EGCG modulates tobacco smoke (TS)-induced inflammatory responses in lung carcinogenesis remain incompletely elucidated.

Purpose

To unravel the molecular mechanisms by which EGCG mitigates TS-induced inflammatory processes in lung carcinogenesis.

Methods

Network pharmacology analysis was conducted to explore the potential target genes of EGCG involved in the inhibition of TS-induced lung cancer inflammation. In vitro and in vivo experiments were conducted to demonstrate EGCG's chemopreventive potential against lung carcinogenesis.

Results

Utilizing data from the US adults, it was uncovered that tea consumption could suppress the inflammatory response in patients with various cancer types. CCL5 (chemokine (CC motif) ligand 5) could function as a core regulator of TS-induced lung cancer cell proliferation, and EGCG exerted beneficial effects. The following experiments revealed that TS upregulated CCL5 expression in H1299 and H226 cells. CCL5 recombinant protein elevated both ROS production and Nrf2 expression to promote lung cancer cell proliferation. EGCG could suppress CCL5-stimulated lung cancer cell proliferation by downregulating Nrf2 expression. In the mouse model, EGCG reduced tumor weight and volume, diminished the levels of CCL5, Ki67, Cyclin D1, PCNA, and Nrf2, and elevated the expression of Keap1 relative to the control group.

Conclusion

EGCG targets CCL5 to inhibit the proliferation of TS-induced lung cancer cells and may serve as a new treatment strategy.