Cryptotanshinone inhibits lung tumor growth by increasing CD4+ T cell cytotoxicity through activation of the JAK2/STAT4 pathway

Man, Yonghong; Yang, Lifang; Zhang, Dongxian; Bi, Yang

doi:10.3892/ol.2016.5123

Cited by 23 publications

(17 citation statements)

References 29 publications

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“…CT could increase the cytotoxicity of CD4 + T cells without affecting the activity of CD8 + T cells. Further investigation indicated that CT activated the JAK 2/STAT 4 pathway in the CD4 + T cells, thereby inhibiting the growth of small cell lung cancer (Yong et al, 2016). Perforin is one of the direct target genes of STAT 4 and is activated by IL-12 (Yamamoto et al, 2002).…”

Section: The Antitumor Function and Mechanism Of Ctmentioning

confidence: 99%

The Anticancer Properties of Tanshinones and the Pharmacological Effects of Their Active Ingredients

Han

Zhou

et al. 2020

Front. Pharmacol.

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Cancer is a common malignant disease worldwide with an increasing mortality in recent years. Salvia miltiorrhiza, a well-known traditional Chinese medicine, has been used for the treatment of cardiovascular and cerebrovascular diseases for thousands of years. The liposoluble tanshinones in S. miltiorrhiza are important bioactive components and mainly include tanshinone IIA, dihydrodanshinone, tanshinone I, and cryptotanshinone. Previous studies showed that these four tanshinones exhibited distinct inhibitory effects on tumor cells through different molecular mechanisms in vitro and in vivo. The mechanisms mainly include the inhibition of tumor cell growth, metastasis, invasion, and angiogenesis, apoptosis induction, cell autophagy, and antitumor immunity, and so on. In this review, we describe the latest progress on the antitumor functions and mechanisms of these four tanshinones to provide a deeper understanding of the efficacy. In addition, the important role of tumor immunology is also reviewed.

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Section: The Antitumor Function and Mechanism Of Ctmentioning

confidence: 99%

The Anticancer Properties of Tanshinones and the Pharmacological Effects of Their Active Ingredients

Han

Zhou

et al. 2020

Front. Pharmacol.

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“…Studies have shown that CTS can inhibit the growth of certain kinds of tumor cells or induce tumor cell apoptosis, including leukemia, breast cancer, prostate cancer, and lung cancer. 9 – 12 Nevertheless, CTS did not affect the survival of noncancerous cells, such as human peripheral blood lymphocytes, 9 human embryonic kidney HEK293 cells, 13 and mouse embryonic fibroblasts. 14 CTS-induced cancer cell death was attributed to cell cycle arrest, 15 , 16 apoptosis, 9 , 12 , 17 and suppression of STAT3 signaling.…”

Section: Introductionmentioning

confidence: 95%

“…Nevertheless, CTS did not affect the survival of noncancerous cells, such as human peripheral blood lymphocytes,9 human embryonic kidney HEK293 cells,13 and mouse embryonic fibroblasts 14. CTS-induced cancer cell death was attributed to cell cycle arrest,15,16 apoptosis,9,12,17 and suppression of STAT3 signaling 9,11–13,18. However, the effect of CTS on human CCA cells has not been previously investigated.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, more attention has been paid to its anticancer effect. Studies have shown that CTS can inhibit the growth of certain kinds of tumor cells or induce tumor cell apoptosis, including leukemia, breast cancer, prostate cancer, and lung cancer 9–12. Nevertheless, CTS did not affect the survival of noncancerous cells, such as human peripheral blood lymphocytes,9 human embryonic kidney HEK293 cells,13 and mouse embryonic fibroblasts 14.…”

Section: Introductionmentioning

confidence: 99%

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Cryptotanshinone induces cell cycle arrest and apoptosis through the JAK2/STAT3 and PI3K/Akt/NFkB pathways in cholangiocarcinoma cells

Wang

Song

et al. 2017

DDDT

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BackgroundCholangiocarcinoma (CCA) is the most common biliary tract malignancy in the world with high resistance to current chemotherapies and extremely poor prognosis. The main objective of this study was to investigate the inhibitory effects of cryptotanshinone (CTS), a natural compound isolated from Salvia miltiorrhiza Bunge, on CCA both in vitro and in vivo and to explore the underlying mechanisms of CTS-induced apoptosis and cell cycle arrest.MethodsThe anti-tumor activity of CTS on HCCC-9810 and RBE cells was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay and colony forming assays. Cell cycle changes were detected by flow cytometric analysis. Apoptosis was detected by annexin V/propidium iodide double staining and Hoechst 33342 staining assays. The efficacy of CTS in vivo was evaluated using a HCCC-9810 xenograft model in athymic nude mice. The expression of key proteins involved in cell apoptosis and signaling pathway in vitro was analyzed by Western blot analysis.ResultsCTS induced potent growth inhibition, S-phase arrest, apoptosis, and colony-forming inhibition in HCCC-9810 and RBE cells in a dose-dependent manner. Intraperitoneal injection of CTS (0, 10, or 25 mg/kg) for 4 weeks significantly inhibited the growth of HCCC-9810 xenografts in athymic nude mice. CTS treatment induced S-phase arrest with a decrease of cyclin A1 and an increase of cyclin D1 protein level. Bcl-2 expression was downregulated remarkably, while Bax expression was increased after apoptosis occurred. Additionally, the activation of JAK2/STAT3 and PI3K/Akt/NFκB was significantly inhibited in CTS-treated CCA cells.ConclusionCTS induced CCA cell apoptosis by suppressing both the JAK2/STAT3 and PI3K/Akt/NFκB signaling pathways and altering the expression of Bcl-2/Bax family, which was regulated by these two signaling pathways. CTS may serve as a potential therapeutic agent for CCA.

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“…In addition, the antitumor property of Tan IIA has been well-documented. Tan IIA effectively reduces the progression of ovarian cancer [ 13 ], gastric cancer [ 14 ], lung tumors [ 15 ], and bladder cancer [ 16 ]. These findings indicate that Tan IIA could be considered as an adjuvant effective drug to control the progression of human tumors.…”

Section: Introductionmentioning

confidence: 99%

Tanshinone IIA reduces SW837 colorectal cancer cell viability via the promotion of mitochondrial fission by activating JNK-Mff signaling pathways

Jieensinue

Zhu

et al. 2018

BMC Cell Biol

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BackgroundMitochondrial homeostasis has been increasingly viewed as a potential target of cancer therapy, and mitochondrial fission is a novel regulator of mitochondrial function and apoptosis. The aim of our study was to determine the detailed role of mitochondrial fission in SW837 colorectal cancer cell viability, mobility and proliferation. In addition, the current study also investigated the therapeutic impact of Tanshinone IIA (Tan IIA), a type of anticancer adjuvant drug, on cancer mitochondrial homeostasis.ResultsThe results of our data illustrated that Tan IIA promoted SW837 cell death, impaired cell migration and mediated cancer proliferation arrest in a dose-dependent manner. Functional investigation exhibited that Tan IIA treatment evoked mitochondrial injury, as witnessed by mitochondrial ROS overproduction, mitochondrial potential collapse, antioxidant factor downregulation, mitochondrial pro-apoptotic protein upregulation, and caspase-9-dependent apoptotic pathway activation. Furthermore, we confirmed that Tan IIA mediated mitochondrial damage by activating mitochondrial fission, and the inhibition of mitochondrial fission abrogated the proapoptotic effects of Tan IIA on SW837 cells. To this end, our results demonstrated that Tan IIA modulated mitochondrial fission via the JNK-Mff pathways. The blockade of the JNK-Mff axis inhibited Tan IIA-mediated mitochondrial fission and promoted the survival of SW837 cells.ConclusionsAltogether, our results identified mitochondrial fission as a new potential target to control cancer viability, mobility and proliferation. Furthermore, our findings demonstrate that Tan IIA is an effective drug to treat colorectal cancer by activating JNK-Mff-mitochondrial fission pathways.Electronic supplementary materialThe online version of this article (10.1186/s12860-018-0174-z) contains supplementary material, which is available to authorized users.

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Cryptotanshinone inhibits lung tumor growth by increasing CD4+ T cell cytotoxicity through activation of the JAK2/STAT4 pathway

Cited by 23 publications

References 29 publications

The Anticancer Properties of Tanshinones and the Pharmacological Effects of Their Active Ingredients

The Anticancer Properties of Tanshinones and the Pharmacological Effects of Their Active Ingredients

Cryptotanshinone induces cell cycle arrest and apoptosis through the JAK2/STAT3 and PI3K/Akt/NFkB pathways in cholangiocarcinoma cells

Tanshinone IIA reduces SW837 colorectal cancer cell viability via the promotion of mitochondrial fission by activating JNK-Mff signaling pathways

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