Several potent antineoplastic agents are used in treatment of cancer. In spite of their strong antitumor activity, most of them are very costly and all of them have certain side effects. Hence there is a need for more economical and less toxic treatment modalities. We are investigating for an effective chemosensitizer which can be used in combination with conventional chemotherapeutic agents used for breast cancer treatment so that the same therapeutic effect can be achieved with minimum toxicity. Our studies have found out a combination involving docetaxel and resveratrol and another one involving 5-flourouracil and curcumin, which can be effectively used in breast cancer cell lines such that low doses of the chemotherapeutic drugs could be used with enhanced cytotoxicity. The signal transduction pathways regulating the synergistic effect are also analyzed.
email : vinodbs@rgcb.res.in

The major objectives of this study were to see whether the plant Wrightia tinctoria has any anticancer activity, to isolate and identify the anticancer principle from the plant and finally to study the signal transduction pathways regulating the anticancer activity of the active principle. The leaf extracts prepared were checked for their cytotoxicity in cancer cells of various origins. Based on these studies, the dichloromethane extract was found to be the most cytotoxic extract and skin cancer cell lines, especially A375, was found to be the most sensitive cell line. But it was not found to toxic to the normal skin cells. We have isolated the active compound and confirmed its purity. The structural characterization of the compound is going on. We have also studied the anticancer properties of the compound by conducting different apoptotic assays and cell cycle analysis. All these studies prove that the compound is inducing cytotoxicity in skin cancer cells through induction of apoptosis. More studies, both in vitro and in vivo are going on to elucidate its molecular mechanism.
jayesh@rgcb.res.in

Natural products in general and medicinal plants in particular, are believed to be an important source of new chemical substances with potential therapeutic efficacy. Utilization of potential medicinal plants with application of sophisticated assays and scientific research methodologies can help in the identification of new effective drugs. My present interests lies in identifying novel anticancer principles with potential activity from plants. It involves studying the cytotoxic effect of crude extracts from selected plants in cancer cells followed by purification of the biologically active component from the crude extracts; explore the anticancer effect of the active principle and the signal transduction pathways regulating its anticancer activity.

Paclitaxel is the most effective anticancer drug ever been isolated from plants. Its major disadvantages are the dose limiting toxicity and unaffordable cost. In vitro and in vivo studies conducted in the lab have already found that cervical cancer cells can be sensitized to paclitaxel treatment when curcumin, is used in combination with it. The common disadvantage of both these compounds is their insolubility in aqueous medium. Recent studies have shown that polymeric nano particle encapsulated formulations of paclitaxel and curcumin is readily dispersed in aqueous media and exhibit all biological activities produced by free paclitaxel and curcumin. We are investigating whether administration of paclitaxel and curcumin in the nano form can enhance the synergistic effect of paclitaxel and curcumin in in vitro and in vivo conditions. We are also investigating whether administration of curcumin in the nano form can improve its chemopreventive efficacy.

Previous in vitro studies conducted in the lab using different breast cancer cells has found out certain synergistic combinations of conventional chemotherapeutic drugs and non-toxic chemosensitizers. It had been found that some of these combinations are having very good anti tumor activity with minimum side effects. Before using these combinations in clinical trials, the efficacy of these combinations must be validated through animal experiments. The present study aims at the in vivo evaluation of these combinations and elucidation of the signalling pathways underlying the antitumor activity of these combinations.

E mail: harithahnair@rgcb.res.in