Caesalpinia pulcherrima Arrests Cell Cycle and Triggers Reactive Oxygen Species‑Induced Mitochondrial‑Mediated apoptosis and Necroptosis via Modulating Estrogen and Estrogen Receptors

Abstract

Objective: The present study was aimed at investigating the chemomodulatory potential of C. pulcherrima flowers in breast cancer and explaining its possible mechanism.Materials and Methods: The cytotoxic potential of ethyl acetate fraction of C. pulcherrima (EAFCP) flower was tested in MCF‑12A (normal breast), MCF‑7 (estrogen receptor [ER] positive), and MDA‑MB‑453 (human epidermal growth factor receptor 2 positive) human breast cancer cells by sulforhodamine B assay. Chemomodulatory potential was evaluated in vivo against N‑methyl‑N‑nitrosourea (MNU)‑induced mammary carcinoma in female Sprague Dawley® rats. The mechanism for anticancer potential was screened by in vitro studies involving Annexin V‑FITC assay (apoptosis), cell cycle patterns, intracellular reactive oxygen species, and mitochondrial membrane potential measurement (FACS based) followed by docking study on estrogen receptor‑alpha (ER‑α).Results: The fractions showed perceptible cell growth inhibition potency (IC50 <50 µg/ml) in MCF‑7 breast cancer cells. In MNU‑treated animals, antioxidant enzymes and histological examination showed statistically significant (P < 0.001) changes. Treatment of MCF‑7 cells with EAFCP reduced cell growth rate by a mechanism associated with both apoptotic and necrotic cell death. Molecular docking study further showed that rutin and catechin have a comparable binding affinity for the ER‑α.Conclusion: In this study, we confirmed that EAFCP was most effective in reducing cell viability, scavenging physiological oxidant species, and causing mitochondria‑mediated apoptosis and necroptosis in MCF‑7 cell by selectively modulating the functions of ER‑α.

Keywords: Antioxidant; breast cancer; estrogen receptor modulator; high‑performance liquid chromatography; histopathology