title: SK&F 96365 induces apoptosis and autophagy by inhibiting Akt-mTOR signaling in A7r5 cells.
abstract: SK&F 96365 has been widely used as an inhibitor of transient receptor potential (TRP) calcium channels in various physiological settings. However, growing evidence suggests that SK&F 96365 affects several cellular and molecular processes via uncharacterized off-target mechanisms. In this study, we showed that SK&F 96365 induces apoptosis and autophagy in A7r5 vascular smooth muscle cells. The combined suppression of apoptosis and autophagy provoked necrosis rather than rescued cell death in the cells treated with SK&F 96365. In addition, we found that SK&F 96365 inhibits Akt-mTOR signaling pathways, which is comparable with the efficacy of other known Akt inhibitors. Our findings suggest that SK&F 96365 can be a useful agent for delineating the molecular mechanisms underlying crosstalk among cell death pathways.
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Sang-Yeob
authors.initials: SY
authors.lastname: Kim
authors.forename: Su-Hwa
authors.initials: SH
authors.lastname: Kim
authors.forename: Chae Ryun
authors.initials: CR
authors.lastname: Lee
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.forename: Jong Kwan
authors.initials: JK
authors.lastname: Park
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
authors.forename: Jung Nyeo
authors.initials: JN
authors.lastname: Chun
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D002121:Calcium Channel Blockers; D007093:Imidazoles; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium