Antiproliferative and apoptotic effects of β-elemene on human hepatoma HepG2 cells

Dai, Zhijun; Tang, Wei; Lu, Wang-Feng; Gao, Jie; Kang, Huafeng; Ma, Xiaolong; Wang, Min; Wang, Xijing; Wang, Wenying

doi:10.1186/1475-2867-13-27

Cited by 54 publications

(20 citation statements)

References 31 publications

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“…There are several canonical strategies for hepatocellular carcinoma treatment, including surgical resection, local ablation, liver transplantation, radiotherapy, chemotherapy, and molecular targeted therapy [ 2 – 4 ]. However, these treatments cause serious side effects sometimes; they are not applicable to all of the patients and demonstrate to be of limited efficacy [ 5 , 6 ]. Therefore, identification of novel antitumor agents from natural products with better effectiveness is an alternative choice for management of hepatocellular carcinoma.…”

Section: Introductionmentioning

confidence: 99%

Huaier Aqueous Extract Induces Hepatocellular Carcinoma Cells Arrest in S Phase via JNK Signaling Pathway

Zhang

et al. 2015

Evidence-Based Complementary and Alternative Medicine

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Huaier aqueous extract, the main active constituent of Huaier proteoglycan, has antihepatocarcinoma activity in experimental and clinical settings. However, the potential and associated antihepatoma mechanisms of Huaier extract are not yet fully understood. Therefore, in this study, we aimed to elucidate the inhibitory proliferation effect of Huaier extract on apoptosis and cycle of HepG2 and Bel-7402 cells. Our data demonstrated that incubation with Huaier extract resulted in a marked decrease in cell viability dose-dependently. Flow cytometric analysis showed that a 48 h treatment of Huaier extract caused cell apoptosis. Typical apoptotic nucleus alterations were observed with fluorescence microscope after Hoechst staining. Immunoblot analysis further demonstrated that Huaier extract activated caspase 3 and PARP. Additionally, Huaier extract inhibited the activity of p-ERK, p-p38, and p-JNK in terms of MAPK. Furthermore, Huaier extract induced HCC cells arrest in S phase and decreased the cycle related protein expression of β-catenin and cyclin D1. Studies with JNK specific inhibitor, SP600125, showed that Huaier extract induced S phase arrest and decreased β-catenin and cyclin D1 expression via JNK signaling pathway. In conclusion, we verify that Huaier extract causes cell apoptosis and induces hepatocellular carcinoma cells arrest in S phase via JNK pathway, which advances our understanding on the molecular mechanisms of Huaier extract in hepatocarcinoma management.

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Section: Introductionmentioning

confidence: 99%

Huaier Aqueous Extract Induces Hepatocellular Carcinoma Cells Arrest in S Phase via JNK Signaling Pathway

Zhang

et al. 2015

Evidence-Based Complementary and Alternative Medicine

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“…A number of studies have investigated the clinical application of TCMs for HCC (13,14), demonstrating that β-elemene, which is present in Rhizoma Curcumae and the main component of cidan, may inhibit the proliferation of HepG2 cells in a time-and dose-dependent manner. The results indicated that β-elemene exhibited positive effects on apoptosis and induced the cell cycle arrest of HepG2 cells in the G2/M phase, while Fas and Fas ligand expression levels were markedly increased (15,16). In addition, a meta-analysis demonstrated that β-elemene improved the effect of lung cancer chemotherapy as an adjunctive treatment (14).…”

Section: Introductionmentioning

confidence: 88%

Cidan inhibits liver cancer cell growth by reducing COX-2 and VEGF expression and cell cycle arrest

Zheng

Xue

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Cidan is a traditional Chinese medicine formula that has been used for >10 years as an antitumor drug. In the present study, the antitumor effect of cidan on hepatocellular carcinoma (HCC) and the underlying molecular mechanisms were investigated. A total of 372 patients with primary HCC, as confirmed by pathological examination in the Eastern Hepatobiliary Surgery Hospital and Beijing Oncology Hospital of Weida TCM, were prospectively enrolled in the study. In total, 92 patients were treated with cidan capsules for three months postoperatively, while 280 patients served as controls. The efficacy of cidan was analyzed by monitoring associated symptoms and liver function tests, including measuring the levels of α-1-fetoprotein, α-L-fucosidase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transferase. In addition, in vivo analysis was performed using mice Hepa1-6 xenograft models, while in vitro studies were performed with SMMC-7721 and CSQT-1 cells; this included cidan-dependent cell viability and migration assays, cell cycle analyses and the evaluation of cidan effects on cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) mRNA transcription rates using quantitative polymerase chain reaction. The postoperative two-year overall survival (77 and 58% for the cidan and control groups, respectively; P<0.01) and disease-free survival (36 and 24% for the cidan and control groups, respectively; P<0.01) rates were superior in the cidan-treated group when compared with the control. In addition, the size and weight of the tumor xenografts in the C57BL/6 mice were significantly reduced in a time-and dose-dependent manner following cidan treatment (P<0.01). Cidan significantly reduced the cell viability of SMMC-7721 and CSQT-1 cells after four and five days when compared with the control (P<0.01). Furthermore, COX-2 and VEGF mRNA expression levels decreased following cidan treatment (P<0.01), and cidan treatment resulted in enhanced G1 and G2/M cell cycle arrest of CSQT-1 cells. Therefore, cidan effectively inhibited cell proliferation, reduced cell viability and downregulated COX-2 and VEGF expression levels in hepatoma cells.

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“…Targeted therapy remains in an early stage of development, indeed, sorafenib has only a modest effect on patient survival ( 5 ). The aforementioned treatments have been demonstrated to be of limited efficacy and are not applicable to all patients ( 6 ). Thus, a novel antitumor agent with improved effectiveness may be a novel choice for the therapeutic treatment of HCC.…”

Section: Introductionmentioning

confidence: 99%

DNMTs inhibitor SGI‑1027 induces apoptosis in Huh7 human hepatocellular carcinoma cells

Sun

Zhang

et al. 2018

Oncol Lett

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SGI-1027, a novel class of relatively stable, highly lipophilic quinoline-based small-molecule inhibitors of DNA methyltransferase enzymes (DNMTs), is able to inhibit DNMTs activity, and reactivate tumor suppressor genes. However, the potential anticancer mechanisms of SGI-1027 on human hepatocellular carcinoma (HCC) cells are still not clearly understood. Thus, the objective of the present study was to clarify the inhibitory effect of SGI-1027 on the cell cycle and apoptosis of the Huh7 cell line. The results revealed that treatment with SGI-1027 resulted in a significant dose-dependent decrease in cell viability. Flow cytometric analysis identified that a 24 h treatment of SGI-1027 resulted in cell apoptosis, and typical apoptotic nucleic alterations were observed with fluorescence microscopy following terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling staining. Immunoblot analysis further demonstrated that SGI-1027 downregulated the expression of B cell lymphoma-2 and upregulated the expression of Bcl-associated X protein. However, no significant alterations of the cell cycle phases were observed. Overall, it is demonstrated that SGI-1027 causes cell apoptosis via the mitochondrial-mediated pathway, which advances current understanding of the molecular mechanisms of SGI-1027 in HCC management.

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Antiproliferative and apoptotic effects of β-elemene on human hepatoma HepG2 cells

Cited by 54 publications

References 31 publications

Huaier Aqueous Extract Induces Hepatocellular Carcinoma Cells Arrest in S Phase via JNK Signaling Pathway

Huaier Aqueous Extract Induces Hepatocellular Carcinoma Cells Arrest in S Phase via JNK Signaling Pathway

Cidan inhibits liver cancer cell growth by reducing COX-2 and VEGF expression and cell cycle arrest

DNMTs inhibitor SGI‑1027 induces apoptosis in Huh7 human hepatocellular carcinoma cells

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