162P - Novel isoxazolyl chromones antagonizing ERα induces anticancer activity via triggering caspase-3 activation

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Clinical research
Presenter Swati Kaushik
Citation Annals of Oncology (2016) 27 (suppl_9): ix46-ix51. 10.1093/annonc/mdw579
Authors S. Kaushik1, M. Rikki2, T.R..S. Kumar3, S. Bhatnagar2
  • 1Cancer Research Lab 1, Rajiv Gandhi Centre for Biotechnology, 695585 - Thiruvananthapuram (Trivandrum)/IN
  • 2Aib, Amity University ACB & PDM, Noida/IN
  • 3Cancer Research Lab1, Rajiv Gandhi Centre for Biotechnology, 695585 - Thiruvananthapuram (Trivandrum)/IN

Abstract

Background

Heterocyclic molecules have been exhaustively explored for their pharmacological importance as antitumour agents. Several polyfunctionally substituted heterocycles such as pyrazoles, isoxazole, pyrimidine, thiazol incorporating oxygen and sulphur heterocycles have been explored in this direction. 2-vinylchromones are rare class of oxygen heterocycles. Natural and synthetic analogues of 2- vinyl chromones have been reported to possess antiallergic, antitumor, antiviral, antioxidant and anti-inflammatory activity. In the present study synthesis of novel analogues of 2-vinyl chromones was undertaken.

Methods

A new class of isoxazolyl chromones 3(a-f) were synthesized and evaluated for their cytotoxic activity against human breast cancer cell lines.

Results

Amongst the analogues synthesized compound 3d exhibited potent antiproliferative activity alone and in combination with ER agonist estradiol (E2) and antagonist 4-hydroxytamoxifen in human breast cancer cell line MCF-7 in dose dependent and time dependent manner. Molecular docking studies have been reported to ascertain the binding site of compounds 3(a-f) in ERα and ERβ. Furthermore, FACS analysis revealed that MCF-7 Cyt C Scat-3 NLS cells treated with compound 3d triggered cells arrest at the G0/G1 phase of the cell cycle. Hoechst staining results indicated that apoptosis was induced when cells were treated with compound 3d. These findings were further corroborated with the results obtained through fluorescence based FRET probe analysis which indicated that compound 3d induced apoptosis via the activation of caspase-3 pathway.

Conclusions

These investigations revealed that isoxazolyl chromones have potential for the development of antitumor drugs towards breast cancer treatment.

Clinical trial indentification

Legal entity responsible for the study

Rajiv Gandhi Centre for Biotechnology, Trivandrum, Kerala, India; Amity University, Noida, India

Funding

Indian Council of Medical Research, New Delhi, India

Disclosure

All authors have declared no conflicts of interest.