Effects of Rhinacanthus nasutus kurz on colon carcinogenesis in mice.

Rhinacanthus nasutus Kurz, a Thai medicinal plant which possess antiproliferative and pro-apoptotic effects on human cancer cells, was examined for chemopreventive potential against colonic neoplasms induced by azoxymethane (AOM) combined with dextran sodium sulfate (DSS) in mice. Male ICR mice were given a single intraperitoneal administration of AOM (10 mg/kg body weight) followed by 2% DSS in their drinking water for a week. Water extract of the roots of R. nasutus (RNR) was given to the animals intragastrically daily in the initiation and promotion phases. The one hundred mice were divided into 8 groups, one group treated with AOM plus DSS serving as a control. Four other groups received AOM/DSS and RNR at 100 or 500 mg/kg body weight for 5 weeks (initiation phase study) and for 14 weeks (promotion phase study). Another two groups were given RNR alone at 100 and 500 mg/kg body weight and the last group was maintained untreated. At the end of the study, we found that the incidence and multiplicity of colonic tumors in mice fed with RNR both at 100 and 500 mg/kg body weight in initiation phase were higher than those in the control group. Moreover, RNR feeding during the promotion phase also gave similar results. Our results suggest that water extract of the roots of R. nasutus Kurz. has no preventive potential against colon carcinogenesis induced by AOM/DSS in mice, rather increasing the incidence of colonic tumors when given during initiation and promotion phases. Further study on RNR should provide more information on mechanisms of its tumor promotion activity.

Synthesis of novel rhinacanthins and related anticancer naphthoquinone esters.

Rhinacanthin-M, -N and -Q, natural products isolated from the medicinal plant Rhinacanthus nasutus, and 39 novel naphthoquinone esters have been synthesized in excellent yield by esterification of naphthoquinone-3-(propan-3'-ols) with benzoic or naphthoic acids. Almost all the naphthoquinone esters that contain a C-3 hydroxy group showed significant cytotoxicities against KB, HeLa, and HepG2 cell lines. In contrast, ester derivatives lacking the C-3 hydroxy group were inactive to the cancer cell lines. Two methyl substituents on the C-2' of propyl chain conferred more potent cytotoxicity than when there is only one or no methyl group. Naphthoate esters exhibited greater cytotoxicity than benzoate esters. Computer modeling has been done to obtain a first look at the mode of action in connection with these observations.

Potent antitumor activity of synthetic 1,2-Naphthoquinones and 1,4-Naphthoquinones.

Rhinacanthone (1) and two 1,2-pyranonaphthoquinones (2,3) were synthesized and found to show very potent cytotoxicity against three cancer cell lines (KB, HeLa and HepG(2)) with IC(50) values of 0.92-9.63 microM, whereas the corresponding hydroxylated derivative 4 had reduced cytotoxicity (IC(50) values of 7.61-24.13 microM). Three 1,2-furanonaphthoquinone derivatives (5-7) were also synthesized with similar cytotoxicity as 1,2-pyranonaphthoquinones. In comparison to 1,2-naphthoquinones, six 1,4-naphthoquinones derivatives fused with pyran ring (8-10) and furan ring (11-13) were synthesized and they showed less cytotoxicity or inactive to the cancer cell lines. Moreover, compound 13 had significant cytotoxicity against HeLa cell line (IC(50) value of 9.25 microM) while it showed no toxic to vero cell.