Cis-diamminedichloroplatinum(II) (CDDP) is considered as one of the most effective antitumor agents for ovarian carcinoma. CDDP-based chemotherapy has clearly improved the response rate in the treatment of ovarian carcinoma, but its clinical potential is often counteracted by intrinsic or acquired resistance and its impact on survival has been only marginal in most cases. Effective chemotherapy for ovarian carcinoma with such CDDP resistance is still not established. Thus, development of antitumor drugs which can be substituted for CDDP is of great importance.Ginseng is one of the most widely used natural tonics in Oriental countries. Odashima et al. 1,2) have reported that a crude fraction of ginsenosides extracted from roots of Panax ginseng CA Meyer induced a phenotypic reverse transformation in cultured Morris hepatoma cells. Ginsenoside Rh 2 (Rh 2 ) is a plant glycoside with a dammarane skeleton, resembling a steroid skeleton, as an aglycone; it has one sugar at C-3 and the capacity to inhibit the growth of and to stimulate melanogenesis in B16 melanoma cells. Recently, we have also demonstrated that i.p. and p.o. administration of Rh 2 inhibited the tumor growth of human ovarian cancer cells inoculated into nude mice and also had an adjuvant effect with CDDP.3, 4) In addition, it has been reported that the long-term p.o. administration of red ginseng augmented natural killer (NK) activity not only in mouse, but also in human. 5,6) The present study extends our previous in vitro and in vivo observations. We now report that p.o. administration of Rh 2 is superior to i.p. administration with regard to antitumor activity and has an apoptosis-inducing effect in addition to an augmenting effect on NK activity.
Improvement of CMI and STAI scores in postmenopausal women suffering climacteric syndromes, particularly fatigue, insomnia and depression, by RG seemed to be brought about in part by effects of RG on stress-related hormones as shown by a decrease in C/D ratio.
Recently two new compounds, ginsenosides Rh1 and Rh2, have been isolated from an ethanol extract of the processed root of Panax ginseng CA Meyer, and Rh2 (but not Rh1) has been found to cause growth inhibition of cultured B16 melanoma cells. We have also demonstrated that Rh2 caused inhibition of cultured human ovarian cancer cell (HRA) proliferation. The effect of oral administration of Rh2 on tumor growth and survival of nude mice bearing HRA cells was examined. Nude mice were inoculated subcutaneously in the right flank with 10(6) HRA cells. After 7 days of tumor inoculation 2 mg/kg cis-diamminedichloroplatinum(II) (cisplatin) was administered intraperitoneally once a week for 5 weeks. In Rh2-treated groups. Rh2 was dissolved in absolute ethanol, adjusted with distilled water to 1, 15, and 120 microM, and 0.4 ml of each concentration was administered orally by canula every day for 90 days, from the next day of tumor inoculation. The tumor volume, hematocrit and body weight were measured every week. On days 56 and 63 after tumor inoculation, the tumor volumes in all groups treated with Rh2 were significantly less than those in an ethanol-treated control group and also in cisplatin treated group. After 70 days, the tumor growth in nude mice treated with 15 microM and 120 microM Rh2 was significantly inhibited compared to that in a cisplatin treated group as well as a control group. Consequently, the survival of nude mice treated with 15 microM and 120 microM Rh2 was also significantly prolonged, compared to that of cisplatin treated mice. No toxic effects were observed in any of the mice.
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