Cryptotanshinone suppresses cell proliferation and glucose metabolism via STAT3/SIRT3 signaling pathway in ovarian cancer cells

Yang, Yufei; Cao, Yue; Chen, Lihua; Liu, Fei; Zhou, Qi; Cheng, Xi; Wang, Ziliang

doi:10.1002/cam4.1691

Cited by 64 publications

(41 citation statements)

References 36 publications

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“…Another study has shown that siRNA mediated STAT3 downregulation suppressed SKOV3 cell growth and arrested the cell cycle in the G1 phase [70]. Several studies have highlighted that plant-derived phytochemicals, such as Pterostilbene, Cryptotanshinone and Curcumin, suppressed STAT3 activation, thereby reduced cancer cell proliferation and have been proposed as possible adjuvants of conventional chemotherapy [71][72][73].…”

Section: Proliferationmentioning

confidence: 99%

Activation of STAT3 and STAT5 Signaling in Epithelial Ovarian Cancer Progression: Mechanism and Therapeutic Opportunity

Sundararajan

Sheu

et al. 2019

Cancers

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Epithelial ovarian cancer (EOC) is the most lethal of all gynecologic malignancies. Despite advances in surgical and chemotherapeutic options, most patients with advanced EOC have a relapse within three years of diagnosis. Unfortunately, recurrent disease is generally not curable. Recent advances in maintenance therapy with anti-angiogenic agents or Poly ADP-ribose polymerase (PARP) inhibitors provided a substantial benefit concerning progression-free survival among certain women with advanced EOC. However, effective treatment options remain limited in most recurrent cases. Therefore, validated novel molecular therapeutic targets remain urgently needed in the management of EOC. Signal transducer and activator of transcription-3 (STAT3) and STAT5 are aberrantly activated through tyrosine phosphorylation in a wide variety of cancer types, including EOC. Extrinsic tumor microenvironmental factors in EOC, such as inflammatory cytokines, growth factors, hormones, and oxidative stress, can activate STAT3 and STAT5 through different mechanisms. Persistently activated STAT3 and, to some extent, STAT5 increase EOC tumor cell proliferation, survival, self-renewal, angiogenesis, metastasis, and chemoresistance while suppressing anti-tumor immunity. By doing so, the STAT3 and STAT5 activation in EOC controls properties of both tumor cells and their microenvironment, driving multiple distinct functions during EOC progression. Clinically, increasing evidence indicates that the activation of the STAT3/STAT5 pathway has significant correlation with reduced survival of recurrent EOC, suggesting the importance of STAT3/STAT5 as potential therapeutic targets for cancer therapy. This review summarizes the distinct role of STAT3 and STAT5 activities in the progression of EOC and discusses the emerging therapies specifically targeting STAT3 and STAT5 signaling in this disease setting.

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Section: Proliferationmentioning

confidence: 99%

Activation of STAT3 and STAT5 Signaling in Epithelial Ovarian Cancer Progression: Mechanism and Therapeutic Opportunity

Sundararajan

Sheu

et al. 2019

Cancers

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“…Moreover, HIF-1α enhances the invasion and migration of OC cells induced by hypoxia ( 33 ). Interestingly, STAT3 promotes the expression of HIF-1α as its upstream molecule ( 17 , 34 ). Here, we found that overexpressing DSCR8 greatly promoted the activation of STAT3/HIF-1α, while overexpressing miR-98-5p reduced STAT3 expression and activation, indicating that DSCR8/miR-98-5p regulates OC development by regulating STAT3/HIF-1α pathway.…”

Section: Discussionmentioning

confidence: 99%

A Positive Feedback Loop of lncRNA DSCR8/miR-98-5p/STAT3/HIF-1α Plays a Role in the Progression of Ovarian Cancer

et al. 2020

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Background Accumulating studies have revealed that long non-coding RNA (lncRNA) and microRNA (miRNA) contribute to ovarian cancer (OC). DSCR8 has been found to mediate hepatocellular carcinoma development, while its role in OC remains to be explored. Methods In this study, lncRNA DSCR8 and miR-98-5p expressions in OC tissues and adjacent non-cancer tissues were determined by reverse transcriptase polymerase chain reaction (RT-PCR). Besides, gain-of-function or loss-of-function assays of DSCR8 and miR-98-5p were conducted on OC cell lines SKOV-3 and A2780. Cell proliferation was detected with Cell Counting Kit (CCK)8 and colony formation assay, and western blot was used to test the apoptotic levels of OC cells. Transwell assay was conducted to examine cell invasion, and the epithelial–mesenchymal transition (EMT) of OC cells was tested by western blot. Moreover, luciferase activity assay and RNA immunoprecipitation (RIP) assay were conducted to verify the relationships between DSCR8 and miR-98-5p, miR-98-5p, and signal transducer and activator of transcription 3 (STAT3). Results DSCR8 was remarkedly increased in OC tissues and associated with poorer survival of OC patients. Overexpressing DSCR8 promoted cell proliferation, invasion, and EMT but inhibited apoptosis. On the other hand, miR-98-5p was downregulated in OC tissues and relieved the progression of OC. Moreover, overexpressed DSCR8 increased the levels of STAT3 and hypoxia inducible factor 1 alpha (HIF-1α) and dampened the functions of miR-98-5p on OC. Pharmaceutical intervention of STAT3 and HIF-1α significantly altered the expressions of DSCR8 and miR-98-5p. Conclusion The present results suggested a positive feedback loop of lncRNA DSCR8/miR-98-5p/STAT3/HIF-α axis in the progression of OC.

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“…In fact, reduced expression of SIRT3 was associated with poor prognosis, whereas intra-tumoral SIRT3 expression was reported as a good prognostic factor in the early stages. So far, the effect of SIRT3 on glucose metabolism has been studied in cancers other than HCC [37][38][39]. Finley et al proposed that SIRT3 loss increases ROS levels and promotes tumorigenesis by altering global cellular metabolism [24].…”

Section: Discussionmentioning

confidence: 99%

Modulation of SIRT3 expression through CDK4/6 enhances the anti-cancer effect of sorafenib in hepatocellular carcinoma cells

Park

Kim

et al. 2020

BMC Cancer

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Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide. The only drug currently approved for clinical use in the treatment of advanced HCC is sorafenib. However, many patients with HCC show reduced sensitivity to sorafenib during treatment. SIRT3, a member of the mammalian sirtuin family, is a tumor suppressor in certain tumor types. However, only few studies have investigated the effects of SIRT3 on tumor prognosis and sorafenib sensitivity in patients with HCC. Here, we aimed to investigate the correlation between SIRT3 expression and glucose metabolism and proliferation in HCC and discover effective compounds that increase endogenous SIRT3 modulation effect of sorafenib. Methods: To determine the correlation between SIRT3 and glucose related proteins, immunostaining was performed with liver cancer tissue using various antibodies. To investigate whether the expression of SIRT3 in HCC is related to the resistance to sorafenib, we treated sorafenib after the modulation of SIRT3 levels in HCC cell lines (overexpression in Huh7, knockdown in HepG2). We also employed PD0332991 to modulate the SIRT3 expression in HCC cell and conducted functional assays. Results: SIRT3 expression was downregulated in high glycolytic and proliferative HCC cells of human patients, xenograft model and HCC cell lines. Moreover, SIRT3 expression was downregulated after sorafenib treatment, resulting in reduced drug sensitivity in HCC cell lines. To enhance the anti-tumor effect of sorafenib, we employed PD0332991 (CDK4/6-Rb inhibitor) based on the correlation between SIRT3 and phosphorylated retinoblastoma protein in HCC. Notably, combined treatment with sorafenib and PD0332991 showed an enhancement of the antitumor effect in HCC cells. Conclusions: Our data suggest that the modulation of SIRT3 by CDK4/6 inhibition might be useful for HCC therapy together with sorafenib, which, unfortunately, has limited efficacy and whose use is often associated with drug resistance.

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Cryptotanshinone suppresses cell proliferation and glucose metabolism via STAT3/SIRT3 signaling pathway in ovarian cancer cells

Cited by 64 publications

References 36 publications

Activation of STAT3 and STAT5 Signaling in Epithelial Ovarian Cancer Progression: Mechanism and Therapeutic Opportunity

Activation of STAT3 and STAT5 Signaling in Epithelial Ovarian Cancer Progression: Mechanism and Therapeutic Opportunity

A Positive Feedback Loop of lncRNA DSCR8/miR-98-5p/STAT3/HIF-1α Plays a Role in the Progression of Ovarian Cancer

Modulation of SIRT3 expression through CDK4/6 enhances the anti-cancer effect of sorafenib in hepatocellular carcinoma cells

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