abyssinone-i and Uterine-Cervical-Neoplasms

Abyssinones I and II are prenylated flavanones existing in plant Erythrina abyssinica showing diverse biological activities including anticancer activities. We synthesized racemic mixtures of these flavanones from corresponding chalcones and herein we report for the first time the molecular mechanisms of cell death, anti-proliferative effect and ability to induce apoptosis in human cervical carcinoma (HeLa) cells. Cytotoxicity was assessed by MTT assay to determine LD50 for prenylated chalcones and their corresponding flavones. Abyssinones promoted apoptosis by up regulation of p53 and Bax, along with down regulation of Bcl-2. Apoptosis induction was mediated through mitochondrial pathway releasing cytochrome c and Apaf-1 into cytosol; associated with activation of caspase-3. Further they were able to decrease the expression of cell proliferation markers PCNA and cyclin D1 indicating anti proliferative activity. These observations demonstrate that abyssinones trigger apoptosis via mitochondrial pathway by activation of caspase-3 and disrupts cell cycle.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Female; Flavonoids; Flow Cytometry; HeLa Cells; Humans; Mitochondria; Molecular Structure; Structure-Activity Relationship; Tumor Cells, Cultured; Uterine Cervical Neoplasms