Inhibitory Effects of Ginsenoside Rh₂ on Tumor Growth in Nude Mice Bearing Human Ovarian Cancer Cells

Abstract

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.

Anticarcinogenic Effect of Panax ginseng C.A. Meyer and Identification of Active Compounds

“…The systemic as well as oral multiple administrations of ginsenoside Rg3 inhibited lung metastasis produced by Bl6-BL6 melanoma and Colon 26-M3.l carcinoma cells in mice. This antimetastatic effect was thought to be associated with the inhibition of the invasion and adhesion by tumor cells as well as suppression of tumor-induced angiogenesis (72)(73)(74)(75)(76)(77). These results dealt mostly with induction of tumor cell differentiation, inhibition of tumor growths, prolongation of animal survival times or inhibition of metastasis.…”

A Comparison and Catalog of Intrinsic Tumor Growth Models

“…Unfortunately, very few data sets exist that allow tumors to grow large enough in order to get a proper estimate of the carrying capacity. We specifically sought out data sets that included data for large populations in order to properly compare the former two models with the latter three (Fujiwara et al, 1993;Takahashi et al, 1992;Murgo, 1985;Richmond et al, 1983;Kisfalvi et al, 2009;Reinmuth et al, 2002;Nakata et al, 1998;Caltagirone et al, 2000;Ricker et al, 2004).…”

Chemistry and Cancer Preventing Activities of Ginseng Saponins and Some Related Triterpenoid Compounds

“…The survival of tumor bearing mice was significantly increased (124 days in the control group, 198 days in the group treated with Rh-2 (120 M/day)), which suggested that the host-mediated immuno-potentiation of ginsenoside Rh-2 activated NK-cells. Nakata et al (29) reported that oral administration of ginsenoside Rh-2 (0.4-1.6 mg/kg/day) showed not only the anti-tumor activity in HRA-transplanted nude mice but also a significant increase of their survival (60 days in the control group, 85 days in the group treated with Rh-2 (0.4 S32mg/kg/day). It is noteworthy that the anti-tumor activity of ginsenoside Rh-2 against HRA cells is superior when orally administered than intra-peritoneally injected.…”