Dr. Babu T. D.

Projects

Analysis on estrogen receptor-β (ERβ) modulation by phytoestrogens of Saracaasoca (Asoka): Preventive and therapeutic strategy for triple negative breast cancer (TNBC)

TNBC, characterized by the lack of expression of estrogen receptors-α (ERα), progesterone receptor (PR) and human epidermal growth factor receptor‐2 (HER-2), is one of the most aggressive subtypes of breast cancers. Due to the lack of specific targets, the classical chemotherapy is still the only established therapeutic option for TNBC with limited success. Even though, ERα is absent, recent studies have detected the second receptor of estrogen, ERβ, an opponent of ERα in 50 to 80% TNBCs and revealed its role in the regulation of initiation, progression and invasiveness. Thus, ERβ is emerging as a new therapeutic target in TNBC. Phytoestrogens are considered as the natural agonists of ERβ and are largely enticed as promising drug candidates due to their role in modulating cell cycle, epigenetic events and inducing apoptosis. Asoka, a well-known medicinal plant is a major constituent of the Ayurvedic medicinal preparation, Asokarishta that is used for various gynaecological disorders. Anticancer properties and phytoestrogens like β-sitosterol, quercetin, kaempferol, catechin have been reported in the plant. Strikingly, in our study, it was observed that Asokais specifically cytotoxic towards ERβ expressing cells but not to ERα. This raises a possibility that the phytoestrogensin Asoka are agonistic to ERβ. Accordingly, the proposed study is aimed to elucidate the role of Asoka in A on ERβmediated death signalling pathways. The study is expected to unravel the role of ERβ signalling in TNBC and in to the identification of potentially effective phytoestrogens against ERα independent cancers, especially TNBCs.

Evaluation of anticancer properties of crystal proteins of Bacillus thuringiensis isolates from the Western Ghats of Kerala


In a DBT sponsored collaborative study with Kerala Agricultural University, a crystal protein belonging to the ‘parasporins’ with cytotoxic effect specifically to cancer cells was detected from a bacterium, Bacillus thuringiensis (bt). This parasporin is the first toxic protein detected in an Indian bt strain. The isolated 29 kD native pro-protein was inactive in nature which when activated by proteolytic cleavage released a 27 kD active protein. The active protein showed a heterogenic cytotoxic spectrum towards various tumor cell lines with no marked cytotoxicity in normal cells. The gene responsible for the protein has been sequenced, cloned and expressed using an expression vector. Thus, a recombinant technology for the massive production of a novel anticancer parasporin was developed. We hope that this specific type of parasporin may emerge as a new class of chemotherapeutics in future.(Completed)
Evaluation of Saracaasoka. Kaempferia rotunda, their substitutes and medicinal preparations with respect to phytochemical and biological properties.

In Ayurveda and other traditional systems of medicine, Saracaasoca is a well-known remedy for gynecological disorders and the bark of this plant is an important raw drug of ‘Ashokaristam’. Due to over exploitation, the natural population of Saracaasoca has been dwindling over the years in the country and the requirement is met through substitutes without any scientific validation. A study conducted in collaboration with KFRI, Peechi has found two plants, Kingiodendronpinnatum and Cynometratravancorica as genuine substitute to Saracaasoca in ‘Ashokaristam’ preparation. Surprisingly, the team is observed that the Arishtam prepared with Polyalthialongifolia which is generally considered as an adulterant of Saracaasoca significantly inhibited the activity of estrogen and retarded the estradiol induced keratinization process in rat uterus even though it is not produced any marked biological activities in its raw form. Thus the study gives a scientific validation for the use these substitutes for the preparation of Asokarishtam. Now we are in stage to recommend the prepared Arishtams with substitutes in clinical application. .(Completed)

Enhancement of the production of promising anticancer agent, baicalein through gamma irradiation in cultures of Scutelleriaspecies seen in Western Ghats of Kerala and its pharmaceutical validation​

A BRNS funded proposal is currently undergoing. The studies aim to enhance the production of promising anticancer agent, baicalein through gamma irradiation in cultures of Scutellaria species seen in Western Ghats of Kerala and its pharmacological validation. Standardisation of in vitro regeneration protocol for mass multiplication of selected Scutellaria plants was achieved and from the source plants bioactive metabolites have been isolated, purified and identified. A comparative assessment of the biological efficacy of purified compounds from callus/plants as well as source plants is being completed. .(Completed)