Cryptotanshinone suppresses the proliferation and induces the apoptosis of pancreatic cancer cells via the STAT3 signaling pathway

Abstract

Abstract. Pancreatic cancer remains a challenging disease worldwide. Cryptotanshinone (CPT) is one of the active constituents of Salvia miltiorrhiza Bunge and exhibits significant antitumor activities in several human cancer cells. However, the efficacy and molecular mechanism of CPT in pancreatic cancer remains to be elucidated. In the present study, the effect of CPT on the proliferation, apoptosis and cell cycle of human pancreatic cancer cell BxPC-3 cells was evaluated. The results demonstrated that CPT inhibited proliferation of the BxPC-3 cells in a concentration-dependent manner, and significantly induced cell apoptosis and cell cycle arrest. The protein levels of cleaved caspase-3, caspase-9 and poly ADP ribose polymerase were upregulated, while the levels of c-myc, survivin and cyclin D1 were downregulated following treatment with CPT. In addition, CPT decreased the activities of signal transducer and activator of transcription 3 (STAT3) and several upstream regulatory signaling pathways after 24 h. However, CPT only inhibited the phosphorylation of STAT3 Tyr705 within 30 min, without marked effects on the phosphorylation of the other proteins. These results suggested that the inhibition of STAT3 activity by CPT was directly and independent of the upstream regulators in human pancreatic cancer. The present study demonstrated that CPT exerts anticancer effects by inducing apoptosis and cell cycle arrest via inhibition of the STAT3 signaling pathway in human BxPC-3 cells.

Cryptotanshinone inhibits human glioma cell proliferation in vitro and in vivo through SHP-2-dependent inhibition of STAT3 activation

“…CTS, as a main active component isolated from the root of Salvia miltiorrhiza Bunge, has been reported to possess a great antiproliferation effect on different cancer cells. 22, 29, 30, 31 In the present study, we confirmed that CTS could significantly inhibit the proliferation of MGs cells in vitro and the growth of intracranial tumor in vivo . The survival period of nude mice bearing intracranial U87 xenografts was obviously extended.…”

Cryptotanshinone inhibits cellular proliferation of human lung cancer cells through downregulation ofIGF-1R/PI3K/Akt signaling pathway

“…Among them, cryptotanshinone (CPT) has been demonstrated to have bioactivities including anti-inflammatory, anti-oxidative stress and antiplatelet aggregation properties (9). Previously, increasing evidence indicates that CPT appears to exert diverse anticancer properties against numerous human cancer cell lines, such as prostate cancer (10), leukemia (11), gliomas (12), hepatic carcinomas (13), pancreatic (14), breast (15), colorectal (16) and melanoma cancer (17). However, only a few studies have reported the anticancer effects of CPT on lung cancer, and more importantly, the underlying mechanism is largely unknown.…”

Comprehensive Live-cell Imaging Analysis of Cryptotanshinone and Synergistic Drug-Screening Effects in Various Human and Canine Cancer Cell Lines

“…Other benefits of Salvia miltiorrhiza include antibacterial (23), immunomodulatory (24) and antioxidant (25) activities. One of the main components of Salvia miltiorrhiza, Cryptotanshinone (CT), has been evaluated in vitro and in vivo as anticancer treatment in human tumor cell lines from different origins, such as, prostate (18,26), breast (26,27,28,29) hepatic (30) and colorectal (18,30,31,32), lung (33), pancreatic (34), kidney (35), glioma (36) and ovarian (37). To date, several human studies have highlighted significant apoptotic effects of CT treatment in cancer cell lines using concentrations of 5 -50 μM (28,32,33,34).…”

“…One of the main components of Salvia miltiorrhiza, Cryptotanshinone (CT), has been evaluated in vitro and in vivo as anticancer treatment in human tumor cell lines from different origins, such as, prostate (18,26), breast (26,27,28,29) hepatic (30) and colorectal (18,30,31,32), lung (33), pancreatic (34), kidney (35), glioma (36) and ovarian (37). To date, several human studies have highlighted significant apoptotic effects of CT treatment in cancer cell lines using concentrations of 5 -50 μM (28,32,33,34). Other effects of CT included cell cycle arrest at G1/G0 phase (30,34,38), and at G2/M phase (33,36,39), inhibition of Cyclin D1 protein expression in different types of cancer (18,31,33,34,35), and downregulation of matrix metallopeptidases (MMP-2/MMP-9), which are responsible for cell invasion and metastasis (37).…”

“…To date, several human studies have highlighted significant apoptotic effects of CT treatment in cancer cell lines using concentrations of 5 -50 μM (28,32,33,34). Other effects of CT included cell cycle arrest at G1/G0 phase (30,34,38), and at G2/M phase (33,36,39), inhibition of Cyclin D1 protein expression in different types of cancer (18,31,33,34,35), and downregulation of matrix metallopeptidases (MMP-2/MMP-9), which are responsible for cell invasion and metastasis (37). Human cancer cells exposed to different concentrations of CT showed inhibition of major signaling pathways that are involved in multiple cellular processes such as, mammalian target of rapamycin (mTOR) in hepatic (30), gastric (30), pancreatic (34), soft sarcoma (38) and prostate (38) cancer.…”