Antitumor progression potential of morusin suppressing STAT3 and NFκB in human hepatoma SK-Hep1 cells

Lin, Wea‐Lung; Lai, Deng-Yu; Lee, Yean‐Jang; Chen, Nai-Fang; Tseng, Tsui‐Hwa

doi:10.1016/j.toxlet.2014.11.031

Cited by 44 publications

(31 citation statements)

References 22 publications

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“…Soonthornsit et al reported that oxyresveratrol at concentrations of 5 and 10 μg/mL inhibited LPS-induced nitrite production and the expression of iNOS and COX-2 [12]. Morusin, a prenylated flavonoid, potentially has neuroprotective, anticancer, antioxidative, and ant-colitis activities [21][22][23][24]. In this study, the anti-inflammatory effect of ethanol extract from the dried root of M. australis (MRE) was evaluated in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 94%

Protective Effects of Morus Root Extract (MRE) Against Lipopolysaccharide-Activated RAW264.7 Cells and CCl4-Induced Mouse Hepatic Damage

Tseng

Lin

Chang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Inflammation is one of the main contributors to chronic diseases such as cancer. It is of great value to identify the potential activity of various medicinal plants for regulating or blocking uncontrolled chronic inflammation. We investigated whether the root extract of Morus australis possesses antiinflammatory and antioxidative stress potential and hepatic protective activity. Methods: The microwave-assisted extractionwere was used to prepare the ethanol extract from the dried root of Morus australis (MRE), including polyphenolic and flavonoid contents. Lipopolysaccharide (LPS)-stimulated RAW264.7 cells was examined the anti-inflammatory and anti-oxidative potential of MRE. CCl₄-induced mouse hepatic damage were performed to detect the hepatic protective potential in vivo. Immunohistochemistry (IHC) and western blot assays were used to detect target proteins. Results: MRE contained approximately 23% phenolic compounds and 3% flavonoids. The major flavonoid component of MRE was morusin. MRE and morusin inhibited lipopolysaccharide-induced production of nitrite and prostaglandin E2 in RAW264.7 cells. MRE and morusin also suppressed the formation of intracellular reactive oxygen species and the expression of iNOS and COX-2. In an in vivo study, a thiobarbituric acid reactive substances assay showed that MRE inhibited CCl₄-induced oxidative stress and expression of nitrotyrosine. MRE also decreased CCl₄-induced hepatic iNOS and COX-2 expression, as well as CCl₄-induced hepatic inflammation and necrosis in mice. Conclusion: MRE exhibited antiinflammatory and hepatic protective activity.

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Section: Discussionmentioning

confidence: 94%

Protective Effects of Morus Root Extract (MRE) Against Lipopolysaccharide-Activated RAW264.7 Cells and CCl4-Induced Mouse Hepatic Damage

Tseng

Lin

Chang

et al. 2018

Cell Physiol Biochem

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“…For HCC, morusin suppressed the invasion of human HCC cells (SK-Hep1) in vitro, decreased their lung colonization in vivo,25 and inhibited human HCC cell (Bel-7402) growth in vitro via apoptosis induction 26. In addition, it exhibited an anticancer effect on murine liver cancer (H22) 27.…”

Section: Discussionmentioning

confidence: 99%

Morusin shows potent antitumor activity for human hepatocellular carcinoma in vitro and in vivo through apoptosis induction and angiogenesis inhibition

Gao¹,

Wang²,

Sun³

et al. 2017

DDDT

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Hepatocellular carcinoma (HCC) is one of the most aggressive cancers with high mortality worldwide. Research and development of novel agents for HCC therapy is in demand, urgently. Morusin has been reported to exhibit potential cytotoxic activity in several cancer cell lines. However, whether it has potential antiangiogenic activity especially in HCC remains unclear. In the current study, we found that morusin exerted growth inhibition effects on human HCC cells (HepG2 and Hep3B) in vitro and human HCC cell (HepG2) xenografts in vivo. Moreover, apoptosis induction was observed in a dose-dependent manner after morusin treatment along with an increase in the expression of active caspase-3 and the Bax/Bcl-2 expression ratio. More importantly, morusin inhibited proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro and downregulated angiogenic proteins in HCC cells and HUVECs. In vivo, tumor angiogenesis was also attenuated after morusin treatment. In addition, morusin suppressed constitutive as well as IL-6-induced STAT3 phosphorylation in HCC cells and corresponding tumor tissues. Overall, morusin has a potential anticancer effect on human HCC cells in vitro and in vivo by inducing apoptosis and inhibiting anti-angiogenesis. The corresponding mechanism might be associated with the attenuation of the IL-6/STAT3 signaling pathway. Morusin might serve as a promising novel anticancer agent in HCC therapy, and requires further study.

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“…Previous studies have indicated that morusin suppresses cancer cell growth, and induces cell death in cervical cancer, hepatoma, glioma and prostate cancer (4)(5)(6)(7)(8)(9). The anticancer activity of morusin is mediated by inhibiting signal transducer and activator of transcription 3 (STAT3) and/or nuclear factor (NF)-κB pathways, which results in apoptosis (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Morusin induces apoptosis by regulating expression of Bax and Survivin in human breast cancer cells

Kang

Kim

et al. 2017

Oncology Letters

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Abstract. Morusin which has been isolated from the root bark of Morus alba L. (Moraceae) has previously demonstrated anticancer activity in various types of cancer cells such as hepatocellular carcinoma, glioma and prostate cancer. However, the effect of morusin on breast cancer cells remains unclear. In the present study, the potential of morusin as an anti-cancer agent in breast cancer was investigated. The results of the present study revealed that the treatment of morusin induced cell death in various human breast cancer cell lines, but exhibited little effect on normal human breast epithelial cells. In Annexin V-propidium iodide double staining assays, morusin significantly increased apoptosis in a dose-dependent manner in human breast cancer cells. The apoptosis marker proteins cleaved caspase 3 and 9 were consistently upregulated following treatment of cells with morusin in a time-and dose-dependent manner. Furthermore, morusin was demonstrated to modulate the expression of the anti-apoptotic protein Survivin and pro-apoptotic protein B-cell lymphoma 2-associated-x protein (Bax) in human breast cancer cells. These results indicate that morusin induces apoptosis by suppressing Survivin and inducing Bax proteins, suggesting that morusin is a potentially effective therapeutic agent for the treatment of patients with breast cancer.

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Antitumor progression potential of morusin suppressing STAT3 and NFκB in human hepatoma SK-Hep1 cells

Cited by 44 publications

References 22 publications

Protective Effects of Morus Root Extract (MRE) Against Lipopolysaccharide-Activated RAW264.7 Cells and CCl4-Induced Mouse Hepatic Damage

Protective Effects of Morus Root Extract (MRE) Against Lipopolysaccharide-Activated RAW264.7 Cells and CCl4-Induced Mouse Hepatic Damage

Morusin shows potent antitumor activity for human hepatocellular carcinoma in vitro and in vivo through apoptosis induction and angiogenesis inhibition

Morusin induces apoptosis by regulating expression of Bax and Survivin in human breast cancer cells

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