Tanshinone IIA enhances the effects of TRAIL by downregulating survivin in human ovarian carcinoma cells

Lin, Jyun-Yi; Ke, Yu-Min; Lai, Jui-Sheng; Ho, Tsing-Fen

doi:10.1016/j.phymed.2015.06.012

Cited by 22 publications

(20 citation statements)

References 28 publications

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“…These studies indicate that survivin is involved in multiple biological processes in EOC. Previous studies have shown that p38 MAPK is required for survivin downregulation in Tanshinone IIA and a high dose of nitric oxide-induced apoptosis in established EOC cell lines [21,35,36]. Our results show that inhibition of p38 MAPK by SB203580 increases survivin protein level in the primary EOC cells, which is consistent with the published results in established EOC cell lines [21,35,36].…”

Section: Discussionsupporting

confidence: 92%

“…Survivin is implicated in cisplatin-induced cytotoxicity in EOC [33,34]. Because published studies showed that p38 MAPK mediates survivin downregulation and apoptosis induced by tanshinone IIA and a high dose of nitric oxide in EOC cells [21,35,36], we examined how carboplatin and SB203580 treatment affects survivin expression in the primary EOC cells. Western blotting showed that SB203580 increased the expression of survivin in all primary EOC cells compared to the DMSO control, albeit to a variable extent (Figure 5).…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have shown that p38 MAPK is required for survivin downregulation in Tanshinone IIA and a high dose of nitric oxide-induced apoptosis in established EOC cell lines [21,35,36]. Our results show that inhibition of p38 MAPK by SB203580 increases survivin protein level in the primary EOC cells, which is consistent with the published results in established EOC cell lines [21,35,36]. However, further experiments are required to determine whether increased survivin contributes to SB203580-mediated increases in viable cells in the primary EOC cells.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacological Inhibition of p38 MAPK by SB203580 Increases Resistance to Carboplatin in A2780cp Cells and Promotes Growth in Primary Ovarian Cancer Cells

Han

Chen

Zhou

et al. 2018

IJMS

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Chemoresistance renders current chemotherapy regimens ineffective against advanced epithelial ovarian cancer (EOC). Carboplatin (the first-line chemotherapeutic agent to treat EOC) induces cell death by regulating multiple signaling pathways. The objective of this study is to identify the signaling pathways that contribute to carboplatin resistance in EOC. To this end, we performed a proteome profiler human phospho-kinase array experiment and compared the phosphorylation profiles between the cisplatin-sensitive A2780s versus its derivative cisplatin-resistant A2780cp cells. The phospho-kinase array revealed that A2780s and A2780cp cells displayed different profiles in basal and carboplatin-induced phosphorylation. Phosphorylation of p38 MAPK was increased by carboplatin more markedly in A2780s cells compared to A2780cp cells. Inhibition of p38 MAPK activity by its specific inhibitor SB203580 increased resistance to carboplatin in A2780cp cells, but not in A2780s cells or in ascites-derived high-grade serous EOC cells. Interestingly, SB203580 increased the number of viable cells in the primary EOC cells, which was concomitant with an increase in survivin expression. In conclusion, inhibition of p38 MAPK by SB203580 increases resistance to carboplatin in A2780cp cells and the number of viable cells in the primary EOC cells, suggesting that pharmacological inhibition of p38 MAPK might not be an effective therapeutic strategy for EOC.

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacological Inhibition of p38 MAPK by SB203580 Increases Resistance to Carboplatin in A2780cp Cells and Promotes Growth in Primary Ovarian Cancer Cells

Han

Chen

Zhou

et al. 2018

IJMS

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“…As a multi-target drug, the molecular targets of Tan IIA include apoptotic-regulating proteins, transcription factors and inflammatory mediators (17,33). In the present study, Tan IIA treatment induced apoptosis, increased the expression of Bax and cleaved caspase-3 and decreased the expression of Bcl-2.…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA inhibits cell proliferation and tumor growth by downregulating STAT3 in human gastric cancer

et al. 2018

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Gastric cancer is the third leading cause of cancer-associated deaths worldwide. Research into the underlying mechanisms of gastric cancer is essential for the development of novel therapeutic agents to improve the prognoses of patients with gastric cancer. Tanshinone IIA (Tan IIA) is the pure extract of Danshen root (Salvia miltiorrhiza) and has been report to inhibit the proliferation of gastric cancer cells; however, the intrinsic underlying mechanisms remain unclear. The aim of the present study was to investigate whether Tan IIA has a direct anti-cancer effect in gastric cancer cells and determine the underlying mechanisms responsible. The results revealed that Tan IIA effectively inhibits proliferation in three human gastric cancer cell lines (SNU-638, MKN1 and AGS) in a time- and dose-dependent manner. Furthermore, Tan IIA treatment induced an increase in apoptosis, B-cell lymphoma (Bcl-2)-associated protein X expression and cleaved caspase-3 levels, as well as a decrease in Bcl-2 expression. Treatment with Tan IIA inhibited Furthermore, treatment with Tan IIA significantly inhibited the phosphorylation of signal transducer and activator of transcription 3 (STAT3), which may be responsible for the changes in apoptosis gene expression. However, overexpression of STAT3 significantly ameliorated the Tan IIA-induced suppression of cell growth and apoptosis. A nude mouse xenograft model was constructed and the results revealed that intraperitoneal Tan IIA treatment for 28 days significantly inhibited tumor growth and STAT3 activation. The results of the present study suggest that Tan IIA exerts potent anti-cancer activity in gastric cancer cells and this effect is mediated by the downregulation of STAT3 activation.

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“…It has been reported that Tanshinone II A inhibit atherosclerotic calcification (Futian et al, 2007). It also relieves the apoptosis of cardiomyocytes (Lin et al, 2015). Additionally, Tanshinone II A has been found to anti-inflammation (Gao et al, 2008).…”

Section: Introductionmentioning

confidence: 98%

Tanshinone II A Relieves Adriamycin-induced Myocardial Injury in Rat Model

Wang¹,

Chai²,

Wang³

et al. 2015

IJC

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As an effective antineoplastic agent, adriamycin (ADR) remains a use for the treatment of cancer. However, it is limited by the serous cardiotoxicity. Tanshinone II A is the main effective component of Salvia miltiorrhiza Bunge which has been used for treatment of cardiovascular diseases. The purpose of this study is to evaluate the protective effect of Tanshinone II A on adriamycin-induced myocardial injury in rat and explore the mechanism of this effect. Male Wistar rats (200 ± 20 g) were divided into three groups, control (CON) group, adriamycin (ADR) group and ADR + Tanshinone II A (TRA) group. At the end of the 4 week treatment period, cardiac function was evaluated by transthoracic echocardiography. Molecular and cellular measurements were performed in atrial muscle to examine histopathological changes, the formation of fibrosis, Inflammation and apoptosis. Cardiac dysfunction was induced by adriamycin, as indicated by significant decreases in ventricular fractional shortening and ejection fraction. This adriamycin-induced cardiac dysfunction was prevented by the treatment of Tanshinone II A. Adriamycin induced pathological changes and fibrosis, activated apoptosis (increased TUNEL index, apoptotic DNA fragmentation,and caspase-3 activity and decreased Bcl-2/Bax ratio), inflammation and suppressed phosphorylation status (eIF2α and PERK) in atrial. All these molecular and cellular alterations induced by ADR were not found in the rats treated with Tanshinone II A. These findings demonstrate clearly that Tanshinone II A protects the cardiomyocytes against the ADR-induced cardiomyopathy by preventing the activation of cardiac fibrosis and apoptosis, and the effects are probably mediated through ERS pathway.

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Tanshinone IIA enhances the effects of TRAIL by downregulating survivin in human ovarian carcinoma cells

Cited by 22 publications

References 28 publications

Pharmacological Inhibition of p38 MAPK by SB203580 Increases Resistance to Carboplatin in A2780cp Cells and Promotes Growth in Primary Ovarian Cancer Cells

Pharmacological Inhibition of p38 MAPK by SB203580 Increases Resistance to Carboplatin in A2780cp Cells and Promotes Growth in Primary Ovarian Cancer Cells

Tanshinone IIA inhibits cell proliferation and tumor growth by downregulating STAT3 in human gastric cancer

Tanshinone II A Relieves Adriamycin-induced Myocardial Injury in Rat Model

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