SKF96365 Inhibits Tumor Proliferation by Inducing Apoptosis and Autophagy in Human Esophageal Squamous Cell Carcinoma

Overview

Journal Int J Genomics

Publisher Wiley

Date 2024 Aug 21

PMID 39165489

Authors

Jiaxin Zhang

Huiqiong Han

Yihan Liu

Jiayao Xu

Daidi Zhang

Wenjia Wang

Yaping Gao

Zhengrui Li

Yanru Qin

Affiliations

Soon will be listed here.

Abstract

Calcium channel blockers are emerging as a new generation of attractive anticancer drugs. SKF96365, originally thought to be a store-operated calcium entry (SOCE) inhibitor, is now often used as a TRPC channel blocker and is widely used in medical diagnostics. SKF96365 has shown antitumor effects on a variety of cancer cell lines. The objective of this study was to investigate the anticancer effect of SKF96365 on esophageal cancer in vivo and in vitro. Cell Counting Kit-8 (CCK-8) and colony formation were used to test the proliferation inhibition of SKF96365 on cell lines. Western blot and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to detect cell apoptosis rates. In addition, we demonstrated the antitumor effect of SKF96365 in vivo in xenografted mice. As a result, SKF96365 significantly inhibited the proliferation of K510, K30, and EC9706 in vitro. SKF96365 induces apoptosis in three cell lines through the poly(adenosine diphosphate-ribose) polymerase (PARP), caspase-9, and BCL-2 pathways in a dose-dependent and time-dependent manner. Moreover, SKF96365 treatment also induced apoptosis and inhibited tumor growth in nude mice. The calcium channel TRPC1 was significantly downregulated by SKF96365. Autophagy was also induced during the treatment of SKF96365. In summary, SKF96365 induces apoptosis (PARP, caspase-9, and BCL-2) and autophagy (LC3-A/B) by inhibiting TRPC1 in esophageal cancer cells, thereby inhibiting tumor growth.

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