Cucurbitacin B induces apoptosis and S phase cell cycle arrest in BEL-7402 human hepatocellular carcinoma cells and is effective via oral administration

Chan, Kin; Meng, Fanbo; Li, Qian; Ho, Cheong Yip; Lam, Tsz Shan; To, Yu; Lee, Wai Him; Li, Miao; Chu, Kee Hung; Toh, Melvin

doi:10.1016/j.canlet.2010.01.029

Cited by 201 publications

(100 citation statements)

References 35 publications

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“…Suppression of transcription factor signal transducer and activator of transcription-3 (STAT3) phosphorylation was associated with the cell killing effect of this natural compound [83] . Chan et al [84] were successful in achieving similar growth inhibitory effects of cucurbitacin B in Bel-7402 cells. Treatment of Bel-7402 cells with cucurbitacin B also induced S phase arrest and apoptosis associated with down regulation of cyclin D1 and cdc-2.…”

Section: Lupeolmentioning

confidence: 97%

“…1-50 μg/mL Eichenmüller et al [80] Failed to induce apoptosis against HepG2 cells ↑survivin; ↑Bcl-2 0.1-50 μg/mL Eichenmüller et al [80] Cucurbitacin B Decreased the viability of HepG2 cells ↑apoptosis; ↓Bcl-2; ↓pSTAT3 10 nmol/L-10 μmol/L Zhang et al [83] Exhibited growth inhibitory effects on Bel-7402 cells ↑apoptosis; ⊥S; ↓cyclin D1; ↓cdc2; ↓c-Raf; ↑ERK 1/2 0.01-1000 μmol/L Chan et al [84] Cucurbitacin D Suppressed the growth of Hep3b cells ↑apoptosis; ↑caspase-3; ↑pJNK 0-10 μmol/L Takahashi et al [85] Cucurbitacin D, I Displayed cytotoxicity against Bel-7402 cells…”

Section: +mentioning

confidence: 99%

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Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

Thoppil

Bishayee²

2011

WJH

278

143

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Despite significant advances in medicine, liver cancer, predominantly hepatocellular carcinoma remains a major cause of death in the United States as well as the rest of the world. As limited treatment options are currently available to patients with liver cancer, novel preventive control and effective therapeutic approaches are considered to be reasonable and decisive measures to combat this disease. Several naturally occurring dietary and non-dietary phytochemicals have shown enormous potential in the prevention and treatment of several cancers, especially those of the gastrointestinal tract. Terpenoids, the largest group of phytochemicals, traditionally used for medicinal purposes in India and China, are currently being explored as anticancer agents in clinical trials. Terpenoids (also called "isoprenoids") are secondary metabolites occurring in most organisms, particularly plants. More than 40 000 individual terpenoids are known to exist in nature with new compounds being discovered every year. A large number of terpenoids exhibit cytotoxicity against a variety of tumor cells and cancer preventive as well as anticancer efficacy in preclinical animal models. This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors. Both in vitro and in vivo effects of these agents and related cellular and molecular mechanisms are highlighted. Potential challenges and future directions involved in the advancement of these promising natural compounds in the chemoprevention and therapy of human liver cancer are also discussed.

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Section: Lupeolmentioning

confidence: 97%

Section: +mentioning

confidence: 99%

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

Thoppil

Bishayee²

2011

WJH

278

143

View full text Add to dashboard Cite

show abstract

“…The diluted aqueous extract of E. elaterium fruits is a traditional anti-inflammatory and analgesic for chronic sinusitis. It also possesses other uses especially the treatment of fever, cancer, liver disorders, jaundice, constipation, hypertension, dropsy, rheumatic diseases, and fungicidal [6,[9][10][11] .…”

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

Effect of ethanolic extract of Ecballium elaterium against Staphylococcus aureus and Candida albicans

Adwan

Salameh

Adwan

2011

Asian Pacific Journal of Tropical Biomedicine

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“…Recently, there has been growing interest in CuB-mediated anticancer activities, mainly mediated through induction of G 2 -M phase cell-cycle arrest, inhibition of the JAK/STAT pathway, and induction of apoptosis (13)(14)(15)(16)(17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

Cucurbitacin B Alters the Expression of Tumor-Related Genes by Epigenetic Modifications in NSCLC and Inhibits NNK-Induced Lung Tumorigenesis

Shukla

Khan

Kumar

et al. 2015

Cancer Prevention Research

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Non-small cell lung cancer (NSCLC) represents almost 85% of total diagnosed lung cancer. Studies have shown that combination of DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors is effective against various cancers, including lung cancer. However, optimizing the synergistic dose regime is very difficult and involves adverse side effects. Therefore, in this study, we have shown that cucurbitacin B (CuB), a single bioactive triterpenoid compound, inhibits both DNMTs and HDACs starting at a very low dose of 60 nmol/L in NSCLC H1299 cells. The CuB-mediated inhibition of DNMTs and HDACs in H1299 cells leads to the reactivation of key tumor suppressor genes (TSG) such as CDKN1A and CDKN2A, as well as downregulation of oncogenes c-MYC and K-RAS and key tumor promoter gene (TPG), human telomerase reverse transcriptase (hTERT). The upregulation of TSGs and downregulation of TPG were consistently correlated with the alterations in their promoter methylation and histone modifications. This altered expression of TPG and TSGs is, at least in part, responsible for the inhibition of cellular proliferation and induction of cellular apoptosis in NSCLC. Furthermore, CuB treatment significantly inhibited the tumor incidence and multiplicity in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice, which was associated with the induction of apoptosis and inhibition of hyperproliferation in the lung tissues. Together, our study provides new insight into the CuB-mediated epigenetic alterations and its chemotherapeutic effects on lung cancer. Cancer Prev Res; 8(6); 552-62. Ó2015 AACR.

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Cucurbitacin B induces apoptosis and S phase cell cycle arrest in BEL-7402 human hepatocellular carcinoma cells and is effective via oral administration

Cited by 201 publications

References 35 publications

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

Effect of ethanolic extract of Ecballium elaterium against Staphylococcus aureus and Candida albicans

Cucurbitacin B Alters the Expression of Tumor-Related Genes by Epigenetic Modifications in NSCLC and Inhibits NNK-Induced Lung Tumorigenesis

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