SKF95365 induces apoptosis and cell-cycle arrest by disturbing oncogenic Ca²⁺ signaling in nasopharyngeal carcinoma cells

Abstract

Background

Aberrant modulation of store-operated calcium ions (Ca²⁺) entry promotes the progression of human malignancies. Previously, we reported that the blockage of store-operated Ca²⁺ entry inhibited epidermal growth factor (EGF)-stimulated migration and distant metastasis in nasopharyngeal carcinoma (NPC) cells. However, the effects of pharmacological blocker on other Ca²⁺ signaling-regulated malignant characteristics in NPC cells remained poorly understood.

Methods

We examined the effects of SKF96365, an inhibitor of store-operated Ca²⁺ channel, on EGF-launched Ca²⁺ signaling in two NPC cell lines. We determined the effects of SKF96365 on cell proliferation, colony formation, apoptosis, and cell-cycle status in vitro. We further elucidated the antitumor activity of SKF96365 in xenograft-bearing mice.

Results

It was found that SKF96365 disturbed the thapsigargin (TG)-stimulated Ca²⁺ release from endoplasmic reticulum and the subsequent Ca²⁺ influx. SKF96365 alone stimulated Ca²⁺ responses merely due to endoplasmic reticulum-released Ca²⁺. SKF96365 promoted cell mortality, inhibited colony formation, and induced apoptosis and cell-cycle arrest, while blunting the EGF-evoked Ca²⁺ signaling. Furthermore, we confirmed that SKF96365 reduced NPC xenograft growth while activating caspase-7-related apoptotic pathway.

Conclusion

SKF96365 exerts multiple antitumor activities through the distraction on the oncogenic Ca²⁺ signaling transduction in NPC cells.

Keywords:

• store-operated Ca²⁺ entry
• EGF signaling
• caspase-7
• caspase-9

Acknowledgments

This study was supported by grants from the National Natural Scientific Foundation of China (numbers 81560438, 81272983, and 81260404), Guangxi Natural Science Foundation (numbers 2015GXNSFCA139014, 2013GXNS-FGA019002), Program for New Century Excellent Talents in University (number NCET-12-0654), Key Project of Health Department of Guangxi Province (number 200919), and Youth Science Foundation of Guangxi Medical University (number GXMUYSF201403).

Disclosure

The authors report no conflicts of interest in this work.