Co‐treatment with ginsenoside Rh2 and betulinic acid synergistically induces apoptosis in human cancer cells in association with enhanced capsase‐8 activation, bax translocation, and cytochrome <i>c</i> release

Li, Qing; Li, Yang; Wang, Xiaoyu; Fang, Xuexun; He, Kan; Guo, Xiao-Xi; Zhuo, Zhan; Sun, Chao; Jin, Yinghua

doi:10.1002/mc.20673

Cited by 45 publications

(34 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies on the molecular pathways related to Rh2-mediated anticancer effect have been limited to the activation of caspase-3 and -8 and the upregulation of pRb2 and TRAIL-RI death receptor (16,17). In order to identify additional molecular pathways participating in the anticancer effect of Rh2, we performed miRNA expression profiling analysis with the aim to detect specific regulators of the Rh2-mediated anticancer properties in NSCLCs.…”

Section: Resultsmentioning

confidence: 99%

“…Rh2 is able to block cell proliferation, cause G1 phase arrest, enhance the activity of capase-3 and induce apoptosis in NSCLC A549 cells (15,16). Additionally, combined treatment with Rh2 and betulinic acid synergistically induces apoptosis in A549 cells (17). Notably, the tumor-inhibiting effects of Rh2 have also been induced by hypersensitizing multidrug-resistant cancer cells (18).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ginsenoside Rh2 mediates changes in the microRNA expression profile of human non-small cell lung cancer A549 cells

An¹,

An²,

Kwon

et al. 2012

Oncology Reports

View full text Add to dashboard Cite

Abstract. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer insensitive to chemotherapy. Efforts are, therefore, directed toward understanding the molecular mechanisms of chemotherapy insensitivity and the development of new anticancer drugs. Ginsenoside Rh2, one of the components in ginseng saponin, has been shown to have anti-proliferative effect on human NSCLC cells and is being studied as a therapeutic drug for NSCLC. microRNAs (miRNAs) are small, non-coding RNA molecules that play a key role in cancer progression and prevention. However, the miRNA portrait of ginsenoside Rh2-treated NSCLC cells has not yet been studied. In this study, we identified a unique set of changes in the miRNA expression profile in response to Rh2 treatment in the human NSCLC cell line A549. Using miRNA microarray analysis, we identified 44 and 24 miRNAs displaying changes in expression greater than 2-fold in Rh2-treated A549 cells. In addition, using an miRNA target prediction program, we discovered that these miRNAs are predicted to have several target genes related to angiogenesis, apoptosis, chromatic modification, cell proliferation and differentiation. Thus, these results may assist in the better understanding of the anticancer mechanism of Rh2 in NSCLC.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rh2 mediates changes in the microRNA expression profile of human non-small cell lung cancer A549 cells

An¹,

An²,

Kwon

et al. 2012

Oncology Reports

View full text Add to dashboard Cite

show abstract

“…A decrease in the mitochondrial inner transmembrane potential is associated with BA treatment, which suggests that the intrinsic mitochondrial pathway is involved in BA-induced apoptosis. The mitochondrial pathway is preceded by the generation of reactive oxygen species (ROS) and is regulated by the Bcl-2 family of proteins, which consists of prosurvival (e.g., Bcl-2, Bcl-XL and Mcl-1) and proapoptotic (Bax, Bad and BH3-only proteins) members [10], [11]. BA has been shown to induce apoptosis in a CD-95 and p53-independent manner by a direct effect on mitochondria [4], [12], [13].…”

Section: Introductionmentioning

confidence: 99%

Proteomic Investigation into Betulinic Acid-Induced Apoptosis of Human Cervical Cancer HeLa Cells

Pang

Zhou

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

Betulinic acid is a pentacyclic triterpenoid that exhibits anticancer functions in human cancer cells. This study provides evidence that betulinic acid is highly effective against the human cervical cancer cell line HeLa by inducing dose- and time-dependent apoptosis. The apoptotic process was further investigated using a proteomics approach to reveal protein expression changes in HeLa cells following betulinic acid treatment. Proteomic analysis revealed that there were six up- and thirty down-regulated proteins in betulinic acid-induced HeLa cells, and these proteins were then subjected to functional pathway analysis using multiple analysis software. UDP-glucose 6-dehydrogenase, 6-phosphogluconate dehydrogenase decarboxylating, chain A Horf6-a novel human peroxidase enzyme that involved in redox process, was found to be down-regulated during the apoptosis process of the oxidative stress response pathway. Consistent with our results at the protein level, an increase in intracellular reactive oxygen species was observed in betulinic acid-treated cells. The proteins glucose-regulated protein and cargo-selection protein TIP47, which are involved in the endoplasmic reticulum pathway, were up-regulated by betulinic acid treatment. Meanwhile, 14-3-3 family proteins, including 14-3-3β and 14-3-3ε, were down-regulated in response to betulinic acid treatment, which is consistent with the decrease in expression of the target genes 14-3-3β and 14-3-3ε. Furthermore, it was found that the antiapoptotic bcl-2 gene was down-regulated while the proapoptotic bax gene was up-regulated after betulinic acid treatment in HeLa cells. These results suggest that betulinic acid induces apoptosis of HeLa cells by triggering both the endoplasmic reticulum pathway and the ROS-mediated mitochondrial pathway.

show abstract

“…It was believed that G-Rh2 is one of the multitarget anti-cancer drugs which could induce apoptosis of cancer cells by canonical signaling pathways, namely the death receptor-dependent and mitochondrial apoptosis pathways. 18,26) According to previous studies, G-Rh2 treatment up-regulated the expression of death receptor Fas in HeLa cells and thus resulted in cleavage of caspase-8 and activation of caspase cascade. 27) In the mitochondrial apoptosis pathway, G-Rh2 administration accelerated the translocation of Bax and Bak from cytosol to mitochondria which consequently stimulated the release of cytochrome c and initiated apoptotic process.…”

Section: Discussionmentioning

confidence: 91%

Ginsenoside Rh2 Inhibited Proliferation by Inducing ROS Mediated ER Stress Dependent Apoptosis in Lung Cancer Cells

Gao

Yan

Cai

2017

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Key words ginsenoside Rh2; lung cancer; apoptosis; reactive oxygen species; endoplasmic reticulum stress Followed by serial biological steps including hyperplasia, metaplasia, dysplasia and in situ carcinoma, similar to other cancers, lung cancer eventually develops its malignancy marked by strong proliferative capacity which is characterized by resistance to apoptosis. 1) Nowadays, lung cancer is still among the top common cancers worldwide. According to the records, lung cancer composes 12.7% of cancer and 18.2% of cancer related death.2) Though the multiple therapies including surgery, radiotherapy and chemotherapy are more and more widely applied to patients, the prognosis of lung cancer is still poor due to its malignant nature. Non-small cell lung cancer (NSCLC) takes approximately 85% of lung cancer cases with less than 20% 5-year survival rate.3) Seeking and identifying new drugs inducing apoptosis may provide us new insight into prevention and treatment of lung cancer.As one of the vital organelles in eukaryotic cells, endoplasmic reticulum (ER) is responsible for directing correct protein folding, calcium homeostasis and lipid metabolism. 4) However, under certain physiological and pathological conditions, the normal functions of ER were impaired by multiple extra-or intra-cellular stimuli, which is referred as ER stress.5) Reactive oxygen species (ROS) is considered as one of the stimuli inducing ER stress. This phenotype is called ROS-mediated ER stress. 6) Many anticancer agents such as chemotherapeutic drugs are believed to induce apoptosis by generating excessive intracellular ROS which is related with unfolded protein response (UPR) in ER to induce ER stress. 7) Numerous investigations supposed that ROS-mediated ER stress could further promote cell apoptosis by activating CCAAT/enhancer binding protein (C/EBP) homologous protein CHOP signaling pathway.8) As a pre-apoptotic factor, CHOP is suggested to activate caspase cascade by inducing cleavage of caspase-12 (rodents) 9) or caspase-4 (human). 10)In recent decades, natural products gradually become new alternatives besides regular therapies. With a long history in traditional medicine in East Asia, ginseng (Panax quinquefolius) is now a very popular herb as medicine or food supplement in the world. 11) Extracted from roots of ginseng, ginsenosides are the main effective components.12) It was suggested in the previous study that among the ginsenosides, ginsenoside Rh2 (G-Rh2, first isolated by Shizuo Odashima 13) ) exhibited various biological and pharmacological activities including anti-inflammation, anti-diabetes and anti-cancer. 14-17)A recent report supposed that G-Rh2 induced colorectal cancer cell apoptosis by inducing excessive intracellular ROS generation.18) Thus, ROS-mediated ER-stress induced apoptosis attracted our attention in investigating gensenoside Rh2's mechanism of anti-proliferation.In this present study, we showed G-Rh2 inhibited proliferation of lung cancer cells by inducing apoptosis. Furthermore, whether ROS-mediated ER-s...

show abstract

Co‐treatment with ginsenoside Rh2 and betulinic acid synergistically induces apoptosis in human cancer cells in association with enhanced capsase‐8 activation, bax translocation, and cytochrome c release

Cited by 45 publications

References 32 publications

Ginsenoside Rh2 mediates changes in the microRNA expression profile of human non-small cell lung cancer A549 cells

Ginsenoside Rh2 mediates changes in the microRNA expression profile of human non-small cell lung cancer A549 cells

Proteomic Investigation into Betulinic Acid-Induced Apoptosis of Human Cervical Cancer HeLa Cells

Ginsenoside Rh2 Inhibited Proliferation by Inducing ROS Mediated ER Stress Dependent Apoptosis in Lung Cancer Cells

Contact Info

Product

Resources

About