Rh2, a compound extracted from ginseng, hypersensitizes multidrug-resistant tumor cells to chemotherapy

Jia, William; Bu, Xuexian; Philips, Don; Yan, Hang; Liu, Guoyu; Chen, Xiaoguang; Bush, Jason A.; Li, Gang

doi:10.1139/y04-049

Cited by 74 publications

(53 citation statements)

References 15 publications

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“…Steroid-like compounds in Chinese medicinal products used for promoting blood circulation Eleven steroid-like compounds were selected for this study as they have been structurally determined and regarded as possible active ingredients in Chinese medicinal products used for the promotion of blood circulation and the treatment of cardiovascular diseases (Table 1) [13][14][15][16][17][18][19][20][21][22][23] . These 11 steroid-like compounds are structurally similar to ouabain, a cardiac glycoside, in the hydrophobic steroidal core regardless the differ- Inhibition of Na + ,K + -ATPase by the selected steroid-like compounds To examine whether the selected steroid-like compounds from Chinese medicinal herbs may be responsible for the effect of promoting blood circulation via the same mechanism triggered by ouabain, a commercial Na + ,K + -ATPase from porcine cerebral cortex was used to evaluate the inhibitory potency of these compounds.…”

Section: Resultsmentioning

confidence: 99%

Steroid-like compounds in Chinese medicines promote blood circulation via inhibition of Na+/K+-ATPase

Chen¹,

Chung²,

et al. 2010

Acta Pharmacol Sin

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Aim: To examine if steroid-like compounds found in many Chinese medicinal products conventionally used for the promotion of blood circulation may act as active components via the same molecular mechanism triggered by cardiac glycosides, such as ouabain. Methods: The inhibitory potency of ouabain and the identified steroid-like compounds on Na + /K + -ATPase activity was examined and compared. Molecular modeling was exhibited for the docking of these compounds to Na + /K + -ATPase. Results: All the examined steroid-like compounds displayed more or less inhibition on Na + /K + -ATPase, with bufalin (structurally almost equivalent to ouabain) exhibiting significantly higher inhibitory potency than the others. In the pentacyclic triterpenoids examined, ursolic acid and oleanolic acid were moderate inhibitors of Na + /K + -ATPase, and their inhibitory potency was comparable to that of ginsenoside Rh2. The relatively high inhibitory potency of ursolic acid or oleanolic acid was due to the formation of a hydrogen bond between its carboxyl group and the Ile322 residue in the deep cavity close to two K + binding sites of Na + /K + -ATPase. Moreover, the drastic difference observed in the inhibitory potency of ouabain, bufalin, ginsenoside Rh2, and pentacyclic triterpenoids is ascribed mainly to the number of hydrogen bonds and partially to the strength of hydrophobic interaction between the compounds and residues around the deep cavity of Na + /K + -ATPase. Conclusion: Steroid-like compounds seem to contribute to therapeutic effects of many cardioactive Chinese medicinal products. Chinese herbs, such as Prunella vulgaris L, rich in ursolic acid, oleanolic acid and their glycoside derivatives may be adequate sources for cardiac therapy via effective inhibition on Na + /K + -ATPase.

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Section: Resultsmentioning

confidence: 99%

Steroid-like compounds in Chinese medicines promote blood circulation via inhibition of Na+/K+-ATPase

Chen¹,

Chung²,

et al. 2010

Acta Pharmacol Sin

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“…Both possess potential anticancer activities and have ginsenosides, such as Rg3 and Rh2, that are active compounds (18)(19)(20). Several ginsenosides have regulated the proliferation of cancer cells in vitro and have sensitized cancer cells to chemotherapy (21)(22)(23). The main constituents in notoginseng root are notoginsenoside R1, and ginsenosides Rb1 and Rg1.…”

Section: Discussionmentioning

confidence: 99%

Chemopreventive effects of Panax notoginseng and its major constituents on SW480 human colorectal cancer cells

Du¹,

He²,

Yuan³

et al. 2007

Int J Oncol

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Abstract. In this study, we evaluated the effects of Panax notoginseng root extract (NGRE) and its major constituents on SW480 human colorectal cancer cells. We used high performance liquid chromatography to determine the contents of major saponins in NGRE. The anti-proliferative effects were evaluated by the cell counting method, and concentrationrelated anti-proliferative effects were observed. At 1.0 mg/ml, NGRE inhibited cell growth by 85.8% (P<0.01), probably linked to the higher concentration of ginsenosides Rb1 and Rg1. The pharmacologic activities of notoginsenoside R1 and ginsenosides Rg1 and Rb1 on the cells were antiproliferative. We tested the effects of NGRE on DNA synthesis by measuring [3 H]-thymidine incorporation. NGRE induced cell apoptosis at 0.5 and 1 mg/ml. Two-day treatment with 300 μM of notoginsenoside R1, ginsenosides Rg1 and Rb1 increased cell apoptosis significantly. Cell cycle and cyclin A assay showed that NGRE arrested cells in the synthesis phase and increased the expression of cyclin A remarkably. NGRE also enhanced the actions of two chemotherapeutic agents, 5-fluorouracil and irinotecan. Cell growth decreased more with the combined treatment of NGRE and 5-fluorouracil (or irinotecan) than with the chemotherapy agent applied alone, suggesting that notoginseng can reduce the dose of 5-fluorouracil (or irinotecan) needed to achieve desired effects. Further in vivo and human trials are warranted to test whether notoginseng is a valuable chemo-adjuvant with clinical validity.

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“…In addition, they may exert their estrogenic influence through either or both of receptor-dependent and receptor-independent mechanisms [33][34][35] . Other studies demonstrate inhibition of breast cancer cell models, particularly by ginseng and its extracts [36][37][38][39][40][41] . Piersen reviewed the conflicting data in detail 42 .…”

Section: Hormone Effectsmentioning

confidence: 99%

“…A study of 20(S)-protopanaxadiol, a major gastrointestinal metabolite of the ginsenosides, suggests that it inhibits estrogen-stimulated gene expression in MCF-7 estrogen receptor (ER)-positive breast cancer cells, inhibits xenograft growth, and enhances the cytotoxicity of tamoxifen in an ER-independent fashion 39 . The Rh2 ginsenoside extract hypersensitizes multidrug-resistant breast cancer cells to paclitaxel 37 . The tumoricidal effect of cisplatin on MCF-7 cells is not attenuated by American ginseng (Panax quinquefolius L.) 41 .…”

Section: Hormone Effectsmentioning

confidence: 99%

“…Laboratory and epidemiologic data indicate that whole ginseng has anti-proliferative activity 37,46,47 , and a clinical study reported improvement in quality of life without increase in cancer recurrence 48 . An abstract from the Mao Clinic (Rochester) presented at the 2007 American Society of Clinical Oncology meeting reported a phase II RCT of North American ginseng (Panax quinquefolium) for cancer patients suffering from fatigue, demonstrating an up to 40% reduction in fatigue in patients on the highest dose level.…”

Section: Hormone Effectsmentioning

confidence: 99%

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Chinese Medicine and Biomodulation in Cancer Patients—Part Two

Sagar

Wong

2008

Current Oncology

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Traditional Chinese Medicine (TCM) is a whole system containing therapeutic interventions that individually induce biomodulation at the physiologic, chemical, and molecular levels. The theory of TCM proposes a synergy between specific interventions selected as part of a care plan based on TCM diagnostic theory. Combining TCM with the modern practice of oncology seems, in conjunction with biomedical interventions (surgery, radiotherapy, chemotherapy, and pharmaceuticals), to have potential advantages through the synergy of biomodulation. Biomodulation approaches are broadly categorized as modification of tumour response and reduction of adverse effects; modulation of immunity; prevention of cancer progression; and enhancement of symptom control. Although the database of preclinical studies is rapidly expanding, good-quality clinical trials are notably scarce.Laboratory studies suggest that some herbs increase the effectiveness of conventional chemotherapy without increasing toxicity. A healthy immune system is necessary for control of malignant disease, and the immune suppression associated with cancer contributes to its progression. Many Chinese herbs contain glycoproteins and polysaccharides (among them, constituents of Coriolus versicolor, Ganoderma lucidum, Grifola frondosa, Astragalus membranaceus, Panax ginseng, and various other medicinal mushrooms) that can modulate metastatic potential and the innate immune system. Phytochemicals such as specific polysaccharides have been shown to boost the innate immune system, especially through interaction with Tolllike receptors in mucosa-associated lymphoid tissue. This intervention can potentially improve the effectiveness of new anticancer vaccines. An increase in virusassociated cancers presents a major public health problem that requires novel therapeutic strategies. A number of herbal therapies have both antiviral activity and the ability to promote immunity, possibly inhibiting the initiation and promotion of virus-associated cancers.The mechanisms learned from basic science should be applied to clinical trials both of specific interventions and of whole-system care plans that safely combine the TCM approach with the conventional biomedical model. In Western medicine, the combination of TCM herbs with drug therapies is controversial, given lack of knowledge concerning whether a drug is favourably enhanced or whether adverse effects occur. Using initial data from the preclinical studies, future clinical research needs to evaluate the combinations, some of which are showing favourable synergy.

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Rh2, a compound extracted from ginseng, hypersensitizes multidrug-resistant tumor cells to chemotherapy

Cited by 74 publications

References 15 publications

Steroid-like compounds in Chinese medicines promote blood circulation via inhibition of Na+/K+-ATPase

Steroid-like compounds in Chinese medicines promote blood circulation via inhibition of Na+/K+-ATPase

Chemopreventive effects of Panax notoginseng and its major constituents on SW480 human colorectal cancer cells

Chinese Medicine and Biomodulation in Cancer Patients—Part Two

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