Dioscin suppresses hepatocellular carcinoma tumor growth by inducing apoptosis and regulation of TP53, BAX, BCL2 and cleaved CASP3

Zhang, Guang‐Xian; Zhang, Xiancheng; Zhang, Ren; Liu, Juan; Zhang, Weici; Zhao, Yongliang; Zhang, Xiaoyuan; Wu, Zhixue; Tan, Yu‐Hui; Wu, Yingya; Du, Baoheng

doi:10.1016/j.phymed.2016.07.003

Cited by 58 publications

(39 citation statements)

References 31 publications

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“…In addition, dioscin shows potent effects against colon cancer, lung cancer, laryngeal cancer, and glioblastoma multiforme (Si et al, ; Wei et al, ). Moreover, dioscin can induce apoptosis and autophagy in Huh‐7 cells (Xu et al, ), suppress cell proliferation in BEL‐7402 cells (Zhang et al, ), and reverses multidrug resistance in human hepatoma HepG2/adriamycin cells (Sun et al, ). However, the effects of dioscin on SMMC7721 and HepG2 cells have not been reported.…”

Section: Introductionmentioning

confidence: 99%

Potent effects of dioscin against hepatocellular carcinoma through regulating TP53‐induced glycolysis and apoptosis regulator (TIGAR)‐mediated apoptosis, autophagy, and DNA damage

Zhang

Han

Chen

et al. 2019

British J Pharmacology

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Background and purpose: Dioscin shows potent effects against cancers. We aimed to elucidate its pharmacological effects and mechanisms of action on hepatocellular carcinoma (HCC) in vivo and in vitro.Experimental approach: Effects of dioscin were investigated in SMMC7721 and HepG2 cells, diethylnitrosamine-induced primary liver cancer in rats, and cell xenografts in nude mice. Isobaric tags for relative and absolution quantitation (iTRAQ)based proteomics was used to find dioscin's targets and investigate its mechanism.Key results: In SMMC7721 and HepG2 cells dioscin markedly inhibited cell proliferation and migration, induced apoptosis, autophagy, and DNA damage. It inhibited DEN-induced primary liver cancer in rats, markedly changed body weights and restored levels of α fetoprotein, alanine transaminase, aspartate transaminase, γ-glutamyltransferase, alkaline phosphatase, and Ki67. It also inhibited growth of xenografts in mice. In SMMC7721 cells, 191 differentially expressed proteins were found after dioscin, based on iTRAQ-based assay. TP53-inducible glycolysis and apoptosis regulator (TIGAR) was identified as being significantly down-regulated by dioscin. Dioscin induced cell apoptosis, autophagy, and DNA damage via increasing expression levels of p53, cleaved PARP, Bax, cleaved caspase-3/9, Beclin-1, and LC3 and suppressing those of Bcl-2, p-Akt, p-mammalian target of rapamycin (mTOR), CDK5, p-ataxia telangiectasia-mutated gene (ATM). The transfection of TIGAR siRNA into SMMC7721 cells and xenografts in nude mice further confirmed that the potent activity of dioscin against HCC is evoked by adjusting TIGAR-mediated inhibition of p53, Akt/mTOR, and CDK5/ATM pathways. Conclusions and implications:The data suggest that dioscin has potential as a therapeutic, and TIGAR as a drug target for treating HCC.

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Section: Introductionmentioning

confidence: 99%

Potent effects of dioscin against hepatocellular carcinoma through regulating TP53‐induced glycolysis and apoptosis regulator (TIGAR)‐mediated apoptosis, autophagy, and DNA damage

Zhang

Han

Chen

et al. 2019

British J Pharmacology

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“…The authors found that its bioavailability after oral administration to rats was very low (0.2%) and sustained prolonged absorption in the intestines, where it remained at high concentrations even after 120 h after administration. Other studies indicated that dioscin has anti-inflammatory properties (Wu et al, 2015) and inhibits proliferation and induces apoptosis in cancer cells (Zhang et al, 2016;Zhao et al, 2016), highlighting this compound as a promising anti-inflammatory and anti-cancer drug.…”

Section: Saponinsmentioning

confidence: 98%

Wild edible plants: Nutritional and toxicological characteristics, retrieval strategies and importance for today's society

Pinela

Ferreira

2017

Food and Chemical Toxicology

146

111

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A B S T R A C TWild edible plants (WEPs) are part of the cultural and genetic heritage of different regions of the world. In times of famine and scarcity, these sources of nutrients and health-promoting compounds have received high importance mainly in rural and suburban areas. Although currently underutilized, WEPs are still consumed traditionally by different communities and are gaining relevance in today's society. However, these foods lack recognition as significant contributors to the human diet in developed areas. This review describes the nutritional value of WEPs from the North-eastern region of Portugal and points out those containing potentially toxic compounds. Several retrieval strategies are presented with the aim of promoting the (re)use, production, commercialization and conservation of WEPs (wild harvested plants and crop wild relatives), and their importance for social, economic and agro-ecological development is highlighted.

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“…TP53 gene mutation is found in many human cancer patients (36,37). Several studies have also shown that TP53 protein plays an important role in HCC, regulating the apoptotic process of cells (38,39). BAX protein is another important protein in the regulation of tumor apoptosis, which can promote the release of cytochrome C and activate Caspase 9 and Caspase 3, which has been confirmed as one of the major proteins regulating apoptosis in HCC (40,41).…”

Section: Discussionmentioning

confidence: 95%

Knockdown expression of <i>MECR</i>, a novel gene of mitochondrial FAS II inhibits growth and colony-formation, promotes apoptosis of hepatocelluar carcinoma cells

Cai

Lin

Xiong

et al. 2019

BST

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Mitochondrial trans-2-enoyl-CoA reductase (MECR) is a protein-coding gene, and the protein encoded by this gene is an oxidoreductase that catalyzes the last step in mitochondrial fatty acid synthesis (mtFASII). Numerous studies have shown disorder of lipid metabolism is closely related with malignance, especially in liver cancer. Through pre-experiment, we found that the expression of MECR gene was highly expressed in hepatocelluar carcinoma (HCC) cell lines in vitro. This suggests that the MECR gene may play a role of oncogene in HCC. Therefore, we conducted a preliminary experimental study on the role of MECR gene in HCC cells in vitro. Objective to explore whether the MECR gene can affect the malignant biological behavior of HCC. We selected HCC cell line BEL-7404 as experimental cell, which involves the highest expression of MECR in the pre-experiment. We constructed MECR knockdwon lentivirus vector, and then infected HCC cell lines to down-regulate MECR expression, and establish negative control group (NC). Through various experiments of cytology, our study showed that knockdown of MECR inhibited cell proliferation and colony formation, promoted apoptosis, and inhibited metastasis in HCC cell lines BEL-7404. MECR might serve as a novel gene therapeutic target for the treatment of HCC. Further study is needed to elucidate the signaling pathway through which MECR functions in HCC.

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Dioscin suppresses hepatocellular carcinoma tumor growth by inducing apoptosis and regulation of TP53, BAX, BCL2 and cleaved CASP3

Cited by 58 publications

References 31 publications

Potent effects of dioscin against hepatocellular carcinoma through regulating TP53‐induced glycolysis and apoptosis regulator (TIGAR)‐mediated apoptosis, autophagy, and DNA damage

Potent effects of dioscin against hepatocellular carcinoma through regulating TP53‐induced glycolysis and apoptosis regulator (TIGAR)‐mediated apoptosis, autophagy, and DNA damage

Wild edible plants: Nutritional and toxicological characteristics, retrieval strategies and importance for today's society

Knockdown expression of <i>MECR</i>, a novel gene of mitochondrial FAS II inhibits growth and colony-formation, promotes apoptosis of hepatocelluar carcinoma cells

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