Furanodiene induces G2/M cell cycle arrest and apoptosis through MAPK signaling and mitochondria-caspase pathway in human hepatocellular carcinoma cells

Xiao, Yu; Yang, Feng‐Qing; Li, Shaoping; Gao, Jian‐Li; Hu, Guoqing; Lao, Sin-Cheng; Conceição, Emilia Leong; Fung, Kwok‐Pui; Wangl, Yi-Tao; Lee, Simon Ming‐Yuen

doi:10.4161/cbt.6.7.4317

Cited by 73 publications

(39 citation statements)

References 24 publications

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“…c, activation of caspase-3 and cleavage of PARP. These effects were associated with the activation of p38 and inactivation of ERK1/2 MAPK signaling cascades [125] . Antiproliferative effects along with redifferentiation were induced in SMMC-7721 human hepatoma cells by two highly oxygenated bisabolane-type sesquiterpenes, namely HOBS1 and HOBS2, isolated from Cremanthodium discoideum.…”

Section: Tetraterpenesmentioning

confidence: 99%

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: Tetraterpenesmentioning

confidence: 99%

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

Thoppil

Bishayee²

2011

WJH

278

143

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“…The decreased expression of antiapoptotic proteins of Bcl-2 family is associated with mitochondrial apoptosis initiation as it was documented by different experimental protocols aimed to find new treatment of acute leukaemia (Jurečeková et al 2011). Previous studies have also documented that G2-phase arrest can be associated with consequent initiation of mitochondrial apoptosis (Strait et al 2005;Xiao et al 2007;Dai et al 2011).…”

Section: Discussionmentioning

confidence: 97%

ABT-737 accelerates butyrate-induced death of HL-60 cells. Involvement of mitochondrial apoptosis pathway

Stefanikova

Kliková²,

Hatok³

et al. 2013

gpb

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Abstract. The aim of presented study was to determine effect of NaBu in combination with ABT-737 on cell survival of leukemic cell line HL-60. In addition, analysis of molecular mechanism of NaBu action with a focus on mitochondrial apoptosis was performed. Both NaBu and ABT-737 are inducing death of HL-60 cells with different kinetics. ABT-737-induced cell death is fast while NaBu-induced death preceded by cell cycle arrest in G2 phase is rather slow. Cell viability was significantly decreased after 48 hours of incubation with 2 and 5 mmol/l of NaBu while it was significantly decreased after 24 hours of incubation with 1 μmol/l of ABT-737 combined with 2 and 5 mmol/l of NaBu. Incubation of HL-60 cells with NaBu was associated with increased level of pro-apoptotic protein BIM EL and decreased levels of anti-apoptotic proteins of Bcl-2 family as well as GRP78 involved in ER stress signalling. It seems that ABT-737 accelerates NaBu-induced death of HL-60 cells due to mitochondrial apoptosis resulting from ABT-737-mediated inhibition of functions and NaBu-induced decrease of the levels of anti-apoptotic Bcl-2 family proteins as well as due to accelerated decrease of GRP78 observed after the treatment of cells with combination of NaBu and ABT-737. The effect of combination of both drugs on survival of HL-60 cells seems to be synergistic at high concentrations of NaBu (2 and 5 mmol/) while it is rather antagonistic at concentrations of NaBu less than 1 mmol/l. Finally, it might be assumed that NaBu is capable to induce cell death with mechanisms independent from mitochondrial apoptosis.

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“…Ezhu (essential oil of Curcuma wenyujin) exhibits an anti-proliferative effect on HepG2 cells by inducing apoptosis (12). This growth inhibition is associated with cell cycle arrest, cytochrome c translocation, caspase 3 activation, Poly-ADP-ribose polymerase (PARP) degradation, and loss of mitochondrial membrane potential (12,13).…”

Section: Discussionmentioning

confidence: 99%

A traditional Chinese medicine formulation consisting of Rhizoma Corydalis and Rhizoma Curcumae exerts synergistic anti-tumor activity

Wang¹

2009

Oncol Rep

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Abstract. Synergy analysis of anticancer agents is an important approach to determining the ratio and/or dose of drugs for clinical combination therapy. However, this method is rarely used to evaluate the composition of traditional Chinese medicine formulation. 'Yanhusuo San' (YHSS), which consists of yanhusuo (Rhizoma Corydalis) and Ezhu (Rhizoma Curcumae), has been an archaic Chinese medicine prescription since the Song dynasty (960-1279 AD). We previously demonstrated that either yanhusuo or ezhu has strong anticancer effect. Herein, we sought to determine the possible synergic effect between these two Chinese herbs. We measured the IC 50 of each herb extract and both extracts at different ratios of doses by MTT assay. Isobologram and combination index (CI) analyses were used to evaluate the synergistic effect of yanhusuo and ezhu in different fixed ratios. Our results indicated that a combination of two herbal extracts exhibits the strongest anticancer cell proliferation effect at the ratio of 3:2 (ezhu to yanhusuo; referred to as E3Y2). Using Boyden Chamber assay, flow cytometry, and fluorescence microscopy analysis, we found that E3Y2 could markedly reduce the cell invasion ability and induce cytochrome c release rather than single use, but E3Y2 could not influence the cell cycle distribution. When the levels of ERK1/2, p-ERK1/2 and p-Rb were determined by Western blot analysis, we found that the E3Y2 significantly suppresses the level of p-ERK. Thus, our studies provide a plausible molecular basis of the synergistic anti-tumor effect of ezhu and yanhusuo.

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Furanodiene induces G2/M cell cycle arrest and apoptosis through MAPK signaling and mitochondria-caspase pathway in human hepatocellular carcinoma cells

Cited by 73 publications

References 24 publications

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

ABT-737 accelerates butyrate-induced death of HL-60 cells. Involvement of mitochondrial apoptosis pathway

A traditional Chinese medicine formulation consisting of Rhizoma Corydalis and Rhizoma Curcumae exerts synergistic anti-tumor activity

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