Comparative in vitro and in silico characterization of anticancer compounds piceatannol, biochanin-A and resveratrol on breast cancer cells

Pardhasaradhi Mathi; Neelima Musunuru; Neelima Musunuru; Mahendran Botlagunta

Articles

Abstract

Pharmacognosy Magazine ,2019,15,66,410-418.

DOI:10.4103/pm.pm_146_19

Published:November 2019

Type:Original Article

Authors:

Author(s) affiliations:

Pardhasaradhi Mathi¹, Neelima Musunuru², Udayapriya Adurthi², Mahendran Botlagunta³
¹Department of Biotechnology, Upstream Process Development, Sun Pharmaceutical Industries, Ltd, Vadodara, Gujarat, India
²Department of Biotechnology, Koneru Lakshmaiah Educational Foundation (K L [Deemed to be University]), Guntur, Andhra Pradesh, India
³Department of Biotechnology, Koneru Lakshmaiah Educational Foundation (K L [Deemed to be University]), Guntur, Andhra Pradesh; Department of Indo American Cancer Research Foundation, Basavatharakam Indo-American Cancer Hospital and Research Institute, Banjara Hills, Hyderabad, Telangana, India

Abstract:

Background: Biochanin-A and Piceatannol are phytochemical constituents extracted from Sophora interrupta. Although both the compounds were isolated from a single plant, these compounds were not compared against anticancer activity. Objective: A systematic comparative analysis of biochanin-A, piceatannol, and resveratrol was performed to investigate cancer cell viability, motility, metabolic changes in Michigan Cancer Foundation-7 breast cancer cells, and structure compound interaction with the vascular endothelial growth factor (VEGF) receptors were studied. Materials and Methods: Cancer cell viability was studied using 3 (4, 5 dimethyl thiazol 2yl) 2, 5 diphenyltetrazo- lium bromide and acridine orange (AO)/ethidium bromide (EtBr) assay. The wound-healing assay was performed by measuring cell migration from the scratch area. Metabolic changes of the compounds in culture conditions were recorded using Fourier-transform infrared (FT-IR) spectroscopy. Molecular docking and dynamic simulations were performed using Schrödinger software. Results: Our results showed that the half-maximal growth inhibitory concentration for biochanin-A is 150 μM/ml and piceatannol and resveratrol showed 150 μM/ml, which is evident from the uptake of AO and EtBr dyes by live/dead cells. Moreover, drug-treated cells were unable to fill the cleared area from the scratch area, which suggests that all compounds effectively inhibit cell motility. FT-IR fingerprint showed a marked difference in the percentage of transition and dynamic structural changes between untreated and treated samples. Strong hydrogen-bond interaction with VEGF receptor-1 (VEGFR1) and VEGFR2 proteins and their interactions were stable throughout the simulation period. Moreover, these compounds inhibited sprouting of a new blood vessel from the chicken aorta and microvessels formation in the in ovo chorioallantoic membrane assay. Conclusion: Taken together, we conclude that anticancer and anti-angiogenic activity, structure-function relationship of biochanin-A is like well-known anticancer compound resveratrol and its metabolic product piceatannol in breast cancer cells.