2016
DOI: 10.1016/j.canlet.2016.01.006
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SKF-96365 activates cytoprotective autophagy to delay apoptosis in colorectal cancer cells through inhibition of the calcium/CaMKIIγ/AKT-mediated pathway

Abstract: Store-operated Ca2+ entry (SOCE) inhibitors are emerging as an attractive new generation of anti-cancer drugs. Here, we report that SKF-96365, an SOCE inhibitor, exhibits potent anti-neoplastic activity by inducing cell-cycle arrest and apoptosis in colorectal cancer cells. In the meantime, SKF-96365 also induces cytoprotective autophagy to delay apoptosis by preventing the release of cytochrome c (cyt c) from the mitochondria into the cytoplasm. Mechanistically, SKF-96365 treatment inhibited the calcium/calmo… Show more

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Cited by 68 publications
(52 citation statements)
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“…Ca 2C could be taken up by the complex of BECN1 and ITPR3 to promote production of ATP then inhibit autophagy. [20][21][22] In colorectal cancer cells, the SOCE inhibitor SKF-96365 induces cytoprotective autophagy, 60 but suppresses autophagy in both epithelial and neuronal cells. 61 Different cell status and complex downstream calcium signaling might account for the controversial results.…”
Section: Discussionmentioning
confidence: 99%
“…Ca 2C could be taken up by the complex of BECN1 and ITPR3 to promote production of ATP then inhibit autophagy. [20][21][22] In colorectal cancer cells, the SOCE inhibitor SKF-96365 induces cytoprotective autophagy, 60 but suppresses autophagy in both epithelial and neuronal cells. 61 Different cell status and complex downstream calcium signaling might account for the controversial results.…”
Section: Discussionmentioning
confidence: 99%
“…As autophagy is also a survival mechanism, one can speculate that autophagy induced by anti‐cancer drugs might contribute to apoptosis resistance . Next, we investigated the cross‐talk between BZML‐induced autophagy and apoptosis in A549 cells or MC in A549/Taxol cells, respectively.…”
Section: Resultsmentioning
confidence: 99%
“…Most studies have reported that autophagy is an important factor for apoptosis resistance . Thus, our study mainly focused on clarifying the interaction between autophagy and MC.…”
Section: Discussionmentioning
confidence: 99%
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