20(&lt;i&gt;S&lt;/i&gt;)-Ginsenoside Rh2 Induces Apoptosis in Human Leukaemia Reh Cells through Mitochondrial Signaling Pathways

Xia, Ting; Wang, Jiancheng; Xu, Wei; Xu, Lü-Hong; Lao, Chonghui; Ye, Qixiang; Fang, Jian‐Pei

doi:10.1248/bpb.b13-00667

Cited by 30 publications

(22 citation statements)

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“…These data suggested that ginsenosides 20(S)-Rh2, Rk2, Rh3, and Rh2-MIX possess anti-cancer effect on the B16F10, MDA-MB-231, and HuH-7 cancer cell lines. This anti-cancer effect was very similar to that disclosed in a previous report [9][10][11][12][13][14]. By contrast, 20(R)- Rh2 did not inhibit B16F10, MDA-MB-231, and HuH-7 cancer cell growth at various concentration ranges within 24 h ( Fig.…”

Section: Scaled-up Production Of Ginsenoside Rh2-mix With Purificationsupporting

confidence: 90%

“…Rh2 can inhibit the growth of many kinds of cancer cells, including breast cancer, prostate cancer, hepatoma, gastric cancer, colon carcinoma, and pancreatic cancer [10]. For example, the ginsenoside 20(S)-Rh2 has anti-cancer effects in the human acute leukemia cell line Reh via a mechanism involving mitochondrial cytochrome c and activation of caspase-9 and caspase-3 [11]. Rh2 was also shown to induce apoptosis of the human hepatoma cell line SK-HEP-1 by the activation of caspase-8 and caspase-9 [12], and to inhibit migration of HepG2 cells by inhibiting the expression of MMP3 at the mRNA and protein levels [13].…”

Section: Introductionmentioning

confidence: 99%

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Production of the Rare Ginsenoside Rh2-MIX (20(S)-Rh2, 20(R)-Rh2, Rk2, and Rh3) by Enzymatic Conversion Combined with Acid Treatment and Evaluation of Its Anti-Cancer Activity

Song

Kim

Choi

et al. 2017

Journal of Microbiology and Biotechnology

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The ginsenoside Rh2 has strong anti-cancer, anti-inflammatory, and anti-diabetic effects. However, the application of ginsenoside Rh2 is restricted because of the small amounts found in Korean white and red ginsengs. To enhance the production of ginsenoside Rh2-MIX (comprising 20()-Rh2, 20()-Rh2, Rk2, and Rh3 as a 10-g unit) with high specificity, yield, and purity, a new combination of enzymatic conversion using the commercial enzyme Viscozyme L followed by acid treatment was developed. Viscozyme L treatment at pH 5.0 and 50°C was used initially to transform the major ginsenosides Rb1, Rb2, Rc, and Rd into ginsenoside F2, followed by acid-heat treatment using citric acid 2% (w/v) at pH 2.0 and 121°C for 15 min. Scale-up production in a 10-L jar fermenter, using 60 g of the protopanaxadiol-type ginsenoside mixture from ginseng roots, produced 24 g of ginsenoside Rh2-MIX. Using 2 g of Rh2-MIX, 131 mg of 20()-Rh2, 58 mg of 20()-Rh2, 47 mg of Rk2, and 26 mg of Rh3 were obtained at over 98% chromatographic purity. Then, the anti-cancer effect of the four purified ginsenosides was investigated on B16F10, MDA-MB-231, and HuH-7 cell lines. As a result, these four rare ginsenosides markedly inhibited the growth of the cancer cell lines. These results suggested that rare ginsenoside Rh2-MIX could be exploited to prepare an anti-cancer supplement in the functional food and pharmaceutical industries.

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Section: Scaled-up Production Of Ginsenoside Rh2-mix With Purificationsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Production of the Rare Ginsenoside Rh2-MIX (20(S)-Rh2, 20(R)-Rh2, Rk2, and Rh3) by Enzymatic Conversion Combined with Acid Treatment and Evaluation of Its Anti-Cancer Activity

Song

Kim

Choi

et al. 2017

Journal of Microbiology and Biotechnology

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“…Ginsenoside Rh2 is a potent anticancer compound targeting multiple cancers [11,13,[15][16][17][18][19]26,27]. Recent reports suggested that ginsenoside Rh2-induced apoptosis in human leukemia cell via mitochondrial signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports suggested that ginsenoside Rh2-induced apoptosis in human leukemia cell via mitochondrial signaling pathways. Following the up-regulation of Bax and Bak, cytochrome c was released from mitochondria into cytoplasm and caspase 3 was activated following cleavage of pro-caspase 8 and procaspase 9 [26,28]. In this study, the overexpression of TNF-α in Rh2-treated HL-60 cells was examined by high-throughput screening using microarray technology.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rh2 inhibits proliferation and induces apoptosis in human leukemia cells via TNF-α signaling pathway

Huang

Peng

Wang

et al. 2016

ABBS

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Ginsenoside Rh2, a triterpene saponin extracted from Panax ginseng, exhibits pharmacological activity against multiple cancers. However, the anticancer mechanism of ginsenoside Rh2 is unclear. In this study, we found that ginsenoside Rh2 effectively inhibits growth and induces apoptosis of HL-60 cells. Using microarray technology, we found that tumor necrosis factor-α (TNF-α) is clearly up-regulated. Furthermore, anti-TNF-α antibody relieved the Rh2-induced HL-60 cell apoptosis via suppression of caspase-8, caspase-9, and caspase-3 activation. In addition, TNF-α up-regulation was also observed in other Rh2-treated cancer cell lines. These results demonstrate that TNF-α plays a key role in ginsenoside Rh2-induced cell apoptosis.

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“…As a step in overcoming this limitation in chemotherapy, medicines prepared from natural traditional Chinese medicine (TCM) are currently being considered as anticancer agents (3,4). In the past decades, a series of studies have demonstrated that many extracted products from natural plants can kill cancer cells including leukemia cells in vitro (5).…”

Section: Introductionmentioning

confidence: 99%

20(S)-ginsenoside Rh2 inhibits the proliferation and induces the apoptosis of KG-1a cells through the Wnt/β-catenin signaling pathway

et al. 2016

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Previous research has shown that total saponins of Panax ginseng (TSPG) and other ginsenoside monomers inhibit the proliferation of leukemia cells. However, the effect has not been compared among them. Cell viability was determined by Cell Counting Kit-8 assay, and ultra-structural characteristics were observed under transmission electron microscopy. Cell cycle distribution and apoptosis were determined by flow cytometry (FCM). Real-time fluorescence quantitative‑PCR, western blotting and immunofluorescence were used to measure the expression of β-catenin, TCF4, cyclin D1 and NF-κBp65. β-catenin/TCF4 target gene transcription were observed by ChIP-PCR assay. We found that 20(S)-ginsenoside Rh2 [(S)Rh2] inhibited the proliferation of KG-1a cells more efficiently than the other monomers. Moreover, (S)Rh2 arrested KG-1a cells in the G0/G1 phase and induced apoptosis. In addition, the levels of β-catenin, TCF4, cyclin D1 mRNA and protein were decreased. The ChIP-PCR showed that (S)Rh2 downregulated the transcription of β-catenin/TCF4 target genes, such as cyclin D1 and c-myc. These results indicated that (S)Rh2 induced cell cycle arrest and apoptosis through the Wnt/β-catenin signaling pathway, demonstrating its potential as a chemotherapeutic agent for leukemia therapy.

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20(<i>S</i>)-Ginsenoside Rh2 Induces Apoptosis in Human Leukaemia Reh Cells through Mitochondrial Signaling Pathways

Abstract: 20(S)-Ginsenoside

Cited by 30 publications

References 36 publications

Production of the Rare Ginsenoside Rh2-MIX (20(S)-Rh2, 20(R)-Rh2, Rk2, and Rh3) by Enzymatic Conversion Combined with Acid Treatment and Evaluation of Its Anti-Cancer Activity

Production of the Rare Ginsenoside Rh2-MIX (20(S)-Rh2, 20(R)-Rh2, Rk2, and Rh3) by Enzymatic Conversion Combined with Acid Treatment and Evaluation of Its Anti-Cancer Activity

Ginsenoside Rh2 inhibits proliferation and induces apoptosis in human leukemia cells via TNF-α signaling pathway

20(S)-ginsenoside Rh2 inhibits the proliferation and induces the apoptosis of KG-1a cells through the Wnt/β-catenin signaling pathway

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20(<i>S</i>)-Ginsenoside Rh2 Induces Apoptosis in Human Leukaemia Reh Cells through Mitochondrial Signaling Pathways

Abstract: 20(S)-Ginsenoside

Cited by 30 publications

References 36 publications

Production of the Rare Ginsenoside Rh2-MIX (20(S)-Rh2, 20(R)-Rh2, Rk2, and Rh3) by Enzymatic Conversion Combined with Acid Treatment and Evaluation of Its Anti-Cancer Activity

Production of the Rare Ginsenoside Rh2-MIX (20(S)-Rh2, 20(R)-Rh2, Rk2, and Rh3) by Enzymatic Conversion Combined with Acid Treatment and Evaluation of Its Anti-Cancer Activity

Ginsenoside Rh2 inhibits proliferation and induces apoptosis in human leukemia cells via TNF-&alpha; signaling pathway

20(S)-ginsenoside Rh2 inhibits the proliferation and induces the apoptosis of KG-1a cells through the Wnt/β-catenin signaling pathway

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Ginsenoside Rh2 inhibits proliferation and induces apoptosis in human leukemia cells via TNF-α signaling pathway