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The Anti-Esophageal Cancer Cell Activity by a Novel tyrosine/phosphoinositide Kinase Inhibitor PP121

The Anti-Esophageal Cancer Cell Activity by a Novel tyrosine/phosphoinositide Kinase Inhibitor PP121

Yi Peng, Yajuan Zhou, Long Cheng, Desheng Hu, Xiaoyi Zhou, Zhaohua Wang, Conghua Xie, Fuxiang Zhou

Biochem Biophys Res Commun. 2015 Sep 11;465(1):137-44.

PMID: 26235881

Abstract:

Here we explored the potential effect of PP121, a novel dual inhibitor of tyrosine and phosphoinositide kinases, against human esophageal cancer cells. We showed that PP121 exerted potent cytotoxic effect in primary (patient-derived) and established (Eca-109, TE-1 and TE-3 lines) esophageal cancer cells, possibly through activating caspase-3-dependnent apoptosis. PP121 was, however, non-cytotoxic to the normal human esophageal epithelial cells (EECs). At the molecular level, we showed that PP121 blocked Akt-mTOR (mammalian target of rapamycin) activation in esophageal cancer cells, which was restored by introducing a constitutively-active Akt (CA-Akt). Yet, CA-Akt only partly inhibited cytotoxicity by PP121 in Eca-109 cells. Importantly, we showed that PP121 inhibited nuclear factor kappa B (NFκB) signaling activation in esophageal cancer cells, which appeared independent of Akt-mTOR blockage. In vivo, oral administration of PP121 remarkably inhibited Eca-109 xenograft growth in nude mice, and significantly improved mice survival. Further, the immunohistochemistry (IHC) and Western blot assays analyzing xenografted tumors showed that PP121 inhibited Akt-mTOR and NFκB activations in vivo. Together, we demonstrate that PP121 potently inhibits esophageal cancer cells in vitro and in vivo, possibly through concurrently inhibiting Akt-mTOR and NFκB signalings.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1092788834-A	PP121		1092788-83-4	Price

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