Signal transducer and activators of transcription 3 regulates cryptotanshinone-induced apoptosis in human mucoepidermoid carcinoma cells

Abstract

Background:Cryptotanshinone (CT) is a biologically active compound from the root of Salvia miltiorrhiza that has been reported to induce apoptosis in various cancer cell lines; but, it has not yet been fully explored in human mucoepidermoid carcinoma (MEC).Objective:Here, we demonstrated the apoptotic effects and its related mechanism in MC-3 and YD-15 human MEC cell lines.Materials and Methods:The effects of CT on apoptotic activity were evaluated by cell proliferation assay, Western blotting, 4’-6-diamidino-2-phenylindole staining, reverse transcription-polymerase chain reaction, and luciferase assay.Results:Our data show that CT treatment of MC-3 cells results in anti-proliferative and apoptotic activities in MC-3 and it is accompanied by a decrease in phosphorylation and dimerization of signal transducer and activators of transcription 3 (STAT3). CT decreased the expression levels of myeloid cell leukemia-1 (Mcl-1) and surviving, whereas Bcl-xL expression was not changed. CT clearly regulates survivin protein at a transcriptional level and alters Mcl-1 through proteasome-dependent protein degradation. In addition, CT-induced apoptotic cell death in YD-15, another human MEC cell line, was associated with the inhibition of STAT3 phosphorylation.Conclusion:These data suggest that CT could be a good apoptotic inducer through modification of STAT3 signaling in human MEC cell lines.

Apoptosis induced by methanol extract of Potentilla�discolor in human mucoepidermoid carcinoma cells through STAT3/PUMA signaling axis

“…Several studies have revealed the critical role of STAT3 in oral cancer development ( 22 , 38 , 39 ). As previously stated from our laboratory, the inhibition of STAT3 by cryptotanshinone or sorafenib clearly induced apoptosis in human MEC cell lines or tumor xenograft ( 40 , 41 ). In the present study, MEPD clearly inhibited STAT3 to induce apoptosis in human MEC cell lines and this observation may support other previous research demonstrating that STAT3 as a promising target for chemotherapy.…”

Cryptotanshinone potentiates the antitumor effects of doxorubicin on gastric cancer cells via inhibition of STAT3 activity

“…These results are consistent with previous studies of other tumors. 42 – 44 Therefore, we postulate that the sensitizing effect of CPT on DOXO-induced apoptosis may be caused by inhibition of STAT3 activity by CPT. The down-regulation of Bcl-xL, Mcl-1, survivin, and XIAP likely indicates an association between the inhibition of STAT3 activity and the capacity of CPT to enhance DOXO-induced apoptosis in gastric cancer cells.…”

Cryptotanshinone Induces Cell Cycle Arrest and Apoptosis of NSCLC Cells through the PI3K/Akt/GSK-3β Pathway

“…Cryptotanshinone (CTT) is a natural product isolated from the root of the Asian medicinal plant, Salvia miltiorrhizabunge . Published studies have reported that CTT has a various pharmacological effects, such as anti-inflammation [ 7 ], anti-diabetes [ 8 ], and anti-cancer effects of CTT [ 9 , 10 , 11 , 12 ]. Recently, a paper has revealed that CTT induced apoptosis in NSCLC through PTEN-mediated inhibition of the PI3K/Akt pathway [ 9 ]; however, no studies have been investigated on the anti-cancer effects of CTT through the PI3K/Akt/ GSK-3β pathway and the comparison with existing anti-cancer drugs.…”