JSI-124 (Cucurbitacin I) Inhibits Tumor Angiogenesis of Human Breast Cancer Through Reduction of STAT3 Phosphorylation

Jia, Qi; Ge, Xia; Huang, Cheng Rong; Wang, Jian Xia; Zhang, Jian

doi:10.1142/s0192415x15500226

Cited by 23 publications

(12 citation statements)

References 19 publications

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“…Cucurbitacin I (JSI-124) is a cell permeable, triterpenoid compound that was shown to specifically suppress tyrosine phosphorylation of STAT3 (23). In the current study, we hypothesized that JSI-124 would be useful to block cross-talk of LCSCs and HSC by inhibiting activation of STAT3.…”

Section: Reversal Of Liver Cancer-associated Stellate Cell-induced Stmentioning

confidence: 99%

Reversal of liver cancer-associated stellate cell-induced stem-like characteristics in SMMC-7721 cells by 8-bromo-7-methoxychrysin via inhibiting STAT3 activation

et al. 2016

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Hepatic stellate cells (HSCs) that are activated by human hepatocellular carcinoma (HCC) cells secrete a variety of cytokines, which are the main component of the HCC microenvironment. We aimed to determine whether 8-bromo-7-methoxychrysin (BrMC) could interfere in cross-talk of the human hepatic stellate cell line LX-2 and liver cancer stem-like cells (LCSLCs) to inhibit the characteristics of LCSLCs endowed with the capacity of sustaining human hepatocellular carcinoma (HCC) self-renewal and progression, and to identify its potential mechanism of action. We found that the levels of fibroblast activation protein (FAP) were augmented in LX-2 cells treated with the conditioned medium of LCSLCs (LCSLC-CM) compared to those cultured with routine medium, indicating that the LCSLC-CM can activate LX-2 cells to become liver cancer-associated stellate cells (LCAHSCs). Furthermore, sphere forming capability of SMMC-7721 cells was enhanced and stem cell-related protein expression was significantly increased following treatment with the conditioned medium of LCAHSCs (LCAHSC-CM). Moreover, the level of p-STAT3 was increased in LX-2 cells treated with LCSLC-CM and BrMC reduced expression of p-STAT3. Combination of BrMC and the selective inhibitor of STAT3 cucurbitacin I (JSI-124) synergistically suppressed the LCSLC characteristics in SMMC-7721 cells. Collectively, our data showed that BrMC inhibited the interaction between LX-2 cells and HCC-derived CSCs, and did so potentially through modulation of the STAT3 pathway. Future therapeutic strategies employing anti-CSC therapy should confirm the potential of cucurbitacin I (JSI-124) and BrMC as potent therapeutic agents.

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Section: Reversal Of Liver Cancer-associated Stellate Cell-induced Stmentioning

confidence: 99%

Reversal of liver cancer-associated stellate cell-induced stem-like characteristics in SMMC-7721 cells by 8-bromo-7-methoxychrysin via inhibiting STAT3 activation

et al. 2016

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“…Since IL-21 can bind to its receptor and phosphorylate STAT3 to initiate the transcription of regulated genes (18), while cucurbitacin I (JSI-124) is able to reduce the phosphorylation level of STAT3 (19), these two factors were used in the present study to regulate the phosphorylation of STAT3. The results showed that the expression of SCLIP was regulated by p-STAT3 levels and the knockdown of SCLIP did not affect the expression of STAT3.…”

Section: Discussionmentioning

confidence: 99%

Expression and functions of the STAT3-SCLIP pathway in chronic myeloid leukemia cells

Zhou

Zheng

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Chronic myeloid leukemia (CML) is a blood cell cancer with increased proliferation of granulocytes. Signal transducers and activators of transcription 3 (STAT3) is an important regulator of CML. To investigate the possible downstream factors of STAT3 and gain more insight into CML-related pathways, this study focused on the superior cervical ganglia protein 10-like protein (SCLIP, or SCG 10-like protein) and analyzed the functions of the STAT3-SCLIP pathway. The effects of STAT3 phosphorylation on SCLIP expression were examined by western blotting. Specific small interfering RNA (siRNA) was then used to knockdown SCLIP in the CML cell line K562 and the expression changes of STAT3 and factors further downstream, namely Bcl-2 and cyclin E1, were detected by RT-qPCR. Cell viability and apoptosis were also analyzed following the knockdown of SCLIP. Results showed a positive association between the phosphorylation of STAT3 and the expression of SCLIP. Knockdown of SCLIP inhibited the viability and induced the apoptosis of K562 cells. Knockdown of SCLIP did not affect the expression of STAT3 mRNA but downregulated the mRNA levels of Bcl-2 and cyclin E1. In conclusion, the results indicate that SCLIP is a direct downstream factor of STAT3, regulates Bcl-2 and cyclin E1 and mediates the viability and apoptosis of CML cells. Consisting of at least these four factors, the STAT3-SCLIP pathway might play critical roles in the regulation of CML. These data provided a more profound understanding of CML-related pathways.

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“…Therefore, they have been used to treat non-suppurative acute mastitis and sebaceous cyst (9). In recent years, some scholars have studied the effects of Yishenguchong decoction, which is constituted by 11 kinds of Chinese herbs, on treating breast cancer (10). Cucurbitacin is a tetracyclic triterpenoid, which is abundant in cucurbitaceous plant (11).…”

Section: Introductionmentioning

confidence: 99%

The anticancer effects of Cucurbitacin I inhibited cell growth of human non‑small cell lung cancer through PI3K/AKT/p70S6K pathway

Zhu¹,

Huang²,

Zhang

et al. 2017

Mol Med Report

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The present study aimed to identify potential anticancer effects of Cucurbitacin I regulators on cell growth of human non‑small cell lung cancer (NSCLC) and to explore their mechanism. The results indicated that the anticancer effects of Cucurbitacin I markedly attenuated cell proliferation, and induced apoptosis in NSCLC. Furthermore, Cucurbitacin I suppressed phosphatidylinositol‑4,5‑bisphosphate 3‑kinase (PI3K), phosphorylation (p)‑AKT and p‑p70S6K pathway in NSCLC. Then, (PI3K) inhibitor increased anticancer effects of Cucurbitacin I on NSCLC. In conclusion, the present results indicated that Cucurbitacin I inhibited cell growth of human NSCLC through PI3K/AKT/p70S6K signaling pathway.

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JSI-124 (Cucurbitacin I) Inhibits Tumor Angiogenesis of Human Breast Cancer Through Reduction of STAT3 Phosphorylation

Cited by 23 publications

References 19 publications

Reversal of liver cancer-associated stellate cell-induced stem-like characteristics in SMMC-7721 cells by 8-bromo-7-methoxychrysin via inhibiting STAT3 activation

Reversal of liver cancer-associated stellate cell-induced stem-like characteristics in SMMC-7721 cells by 8-bromo-7-methoxychrysin via inhibiting STAT3 activation

Expression and functions of the STAT3-SCLIP pathway in chronic myeloid leukemia cells

The anticancer effects of Cucurbitacin I inhibited cell growth of human non‑small cell lung cancer through PI3K/AKT/p70S6K pathway

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