title: Synthetic racemates of abyssinone I and II induces apoptosis through mitochondrial pathway in human cervix carcinoma cells.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Vittal Mallya Scientific Research Foundation, BTM II Stage, Bangalore 560076, India.
authors.forename: Krishna Kumar L
authors.initials: KK
authors.lastname: Samaga
authors.affiliation: Chemistry Division, Vittal Mallya Scientific Research Foundation, BTM II Stage, Bangalore 560076, India.
authors.forename: Gudapati Venkateshwara
authors.initials: GV
authors.lastname: Rao
authors.affiliation: Chemistry Division, Vittal Mallya Scientific Research Foundation, BTM II Stage, Bangalore 560076, India.
authors.forename: G
authors.initials: G
authors.lastname: Chandrashekara Reddy
authors.affiliation: Department of Biological Sciences, Vittal Mallya Scientific Research Foundation, BTM II Stage, Bangalore 560076, India.
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Kush
authors.affiliation: Department of Biological Sciences, Vittal Mallya Scientific Research Foundation, BTM II Stage, Bangalore 560076, India. Electronic address: latha@vmsrf.org.
authors.forename: Latha
authors.initials: L
authors.lastname: Diwakar
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005419:Flavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; C541239:abyssinone I; C511702:abyssinone II
keywords: Abyssinones; Apoptosis; Cervical cancer; Flavonoids; HeLa; Prenylated flavonoids