Downregulation of survivin and activation of caspase-3 through the PI3K/Akt pathway in ursolic acid-induced HepG2 cell apoptosis

Tang, Cong; Lu, Yun-hua; Xie, Jinghang; Wang, Fen; Zou, Jianing; Yang, Jia-Sen; Xing, Yingying; Xi, Tao

doi:10.1097/cad.0b013e328327d476

Cited by 88 publications

(60 citation statements)

References 29 publications

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“…The activated ERK was found to cause the malignant transformation of cells by activating the oncogenes through transcription regulation and play an important role in cell growth, development, division, death and malignant transformation [8][9][10] . UA has recently drawn a great deal of attention for its effects on cancer cells, including inhibition of tumor cell growth and induction of apoptosis [11][12][13][14][15][16] . In this study, we found that UA could inhibit the proliferation of the CAOV3 cells in a concentration-dependent manner and the ERK activity was decreased at the same time in the cells treated with different concentrations of UA.…”

Section: Discussionmentioning

confidence: 99%

Effects of ursolic acid on the proliferation and apoptosis of human ovarian cancer cells

Wang

et al. 2009

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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This study examined the effects of ursolic acid (UA) on the proliferation and apoptosis of a human ovarian cancer cell line, CAOV3. The CAOV3 cells were cultured in the RPMI 1640 media and treated with different concentrations of UA (0, 10, 20, 40 micromol/L). The proliferation rate of the CAOV3 cells was determined by MTT assay. The apoptosis rate was measured by flow cytometry. ERK activity was detected by immunoprecipitation and the expressions of p-ERK1/2, MKP-1, Bax and Bcl-2 by Western blotting. The results showed that the proliferation rate was significantly decreased in the cells treated with UA as compared with that in the non-treated cells (P<0.05). The intracellular ERK activity and p-ERK1/2 expression were also reduced in the UA-treated cells, while the MKP-1 expression was elevated. Moreover, the apoptosis was found in the CAOV3 cells exposed to UA; the Bax expression was increased and the Bcl-2 expression decreased. The apoptosis rate in the UA-treated cells was much higher than that in the non-treated cells (P<0.05). It is concluded that UA can inhibit the proliferation of CAOV3 cells by suppressing the ERK activity and the expression of p-ERK1/2. And it can also induce the apoptosis of the CAOV3 cells by up-regulating the Bax expression and down-regulating the Bcl-2 expression.

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Section: Discussionmentioning

confidence: 99%

Effects of ursolic acid on the proliferation and apoptosis of human ovarian cancer cells

Wang

et al. 2009

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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“…PI3K/AKT pathway was reported to play an important role in cancer proliferation and migration. Previous studies indicated the role of PI3K/AKT pathway in the development and progression of HCC cells, mainly reflected in the mechanism of liver cancer cell proliferation, differentiation and apoptosis (20)(21)(22). The effect of EGCG on PI3K/AKT pathway in carcinogenesis, progression and metastasis in various type of tumors, have been widely studied in breast cancer (23), pancreatic cancer (8), endometrial cancer (24) and thyroid carcinoma (25).…”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin-3-gallate inhibits cell growth, induces apoptosis and causes S phase arrest in hepatocellular carcinoma by suppressing the AKT pathway

Shen

Zhang

Yan

et al. 2014

International Journal of Oncology

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Abstract. Epigallocatechin-3-gallate (EGCG) has been shown to inhibit the growth and induce apoptosis of certain cancer cells. The aim of this study was to determine the role of EGCG in hepatocellular carcinoma (HCC) and the underlying mechanism(s) thereof. MTT assay was used to determine the cell growth inhibition by EGCG. Apoptosis induced by EGCG was investigated by both AO/EB staining and flow cytometry. The cell cycle distribution was analyzed by flow cytometry. The mRNA levels of the AKT pathway were analyzed by quantitative PCR. The expression of AKT and its phosphorylation at Ser473 were detected by western blotting. The IC 50 of EGCG at 48 h for HepG2, SMMC7721 and SK-hep1 cells were 74.7, 59.6 and 61.3 µg/ml, respectively. Significantly higher proportion of SMMC7721 cells entered the S phase upon treatment with EGCG for 48 h compared with control cells. EGCG decreased the mRNA levels of PI3K, AKT and NF-κB. The protein levels of AKT decreased and its phosphorylation at Ser473 was downregulated with EGCG treatment. EGCG inhibited growth by affecting the cell cycle and induced apoptosis in different HCC cells by downregulating PI3K/ AKT activity. The results suggest the potential of EGCG as an anticancer agent in the prevention or treatment of HCC.

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“…UA-mediated downregulation of cyclooxygenase-2 and upregulation of HSP105 provided additional mechanisms [109] . UA was also found to exert antiproliferative effects against HepG2 cells through activation of apoptosis accompanied by a significant decrease in Bcl-2 and survivin expression [110] . Two recent studies confirmed the anti-tumor effects of UA using HepG2 as well as additional cell lines, such as Hep3B, Huh7 and HA22T.…”

Section: Lupeolmentioning

confidence: 99%

“…3.125-100 μmol/L Tian et al [109] Suppressed the proliferation of HepG2 cells ↑apoptosis; ↑p53; ↓Bcl-2; ↓survivin; ↑caspase-3; ↓PI3K/Akt 5-80 μmol/L Tang et al [110] Decreased the viability of HepG2, Hep3B, Huh7 and HA22T cells ↑apoptosis; ↓∆Ψm; ↑caspase-3, -8; ↓Na [107] Reduced the viability of Huh7 cells ↑apoptosis; ↓∆Ψm; ↑Bax; ↓Bcl2; ↑cyt. c; ↑ caspase-3, -9; ↓NF-κB; ↓XIAP 20-100 μmol/L Shyu et al [108] Waltonitone Conferred inhibitory effects on the growth of BEL-7402 cells ↑apoptosis; ↑caspase-3, -8, -9; ↑Bax; ↑cyt.…”

Section: Lupeolmentioning

confidence: 99%

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

Thoppil

Bishayee²

2011

WJH

265

134

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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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Downregulation of survivin and activation of caspase-3 through the PI3K/Akt pathway in ursolic acid-induced HepG2 cell apoptosis

Cited by 88 publications

References 29 publications

Effects of ursolic acid on the proliferation and apoptosis of human ovarian cancer cells

Effects of ursolic acid on the proliferation and apoptosis of human ovarian cancer cells

Epigallocatechin-3-gallate inhibits cell growth, induces apoptosis and causes S phase arrest in hepatocellular carcinoma by suppressing the AKT pathway

Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

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