Rh2, a compound extracted from ginseng, hypersensitizes multidrug-resistant tumor cells to chemotherapy.
Rh2 is a ginsenoside extracted from ginseng that has drawn attention in a few laboratories in Asian countries because of its potential tumor-inhibitory effect. In the present study, we tested Rh2 on many tumor-cell lines for its effects on cell proliferation, induction of apoptosis, and potential interaction with conventional chemotherapy agents. Our results showed that Rh2 inhibited cell growth by G1 arrest at low concentrations and induced apoptosis at high concentrations in a variety of tumor-cell lines, possibly through activation of caspases. The growth arrest and apoptosis may be mediated by 2 separate mechanisms. Apoptosis is not dependent on expression of the wild-type p53 nor the caspase 3. In addition, the apoptosis induced by Rh2 was mediated through glucocorticoid receptors. Most interestingly, Rh2 can act either additively or synergistically with chemotherapy drugs on cancer cells. Particularly, it hypersensitized multidrug-resistant breast cancer cells to paclitaxel. These results suggest that Rh2 possesses strong tumor-inhibiting properties, and potentially can be used in treatments for multidrug-resistant cancers, especially when it is used in combination with conventional chemotherapy agents.
Jia
William W-G
WW
Department of Surgery, University of British Columbia, Vancouver, Canada. wjia@interchange.bc.ca
Bu
Xuexian
X
Philips
Don
D
Yan
Hang
H
Liu
Guoyu
G
Chen
Xiaoguang
X
Bush
Jason A
JA
Li
Gang
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008942:Mitoxantrone / Q000494:pharmacology; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D017239:Paclitaxel / Q000494:pharmacology; D005894:Panax / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D036145:Ginsenosides; D010936:Plant Extracts; D011965:Receptors, Glucocorticoid; D016159:Tumor Suppressor Protein p53; C055305:ginsenoside Rh2; D008942:Mitoxantrone; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D017239:Paclitaxel