Acovenoside A Induces Mitotic Catastrophe Followed by Apoptosis in Non-Small-Cell Lung Cancer Cells

  • J Nat Prod. 2017 Dec 22;80(12):3203-3210. doi: 10.1021/acs.jnatprod.7b00546.
Menna El Gaafary  1  2 ,  Shahira M Ezzat  1  3 ,  Abeer M El Sayed  1 ,  Omar M Sabry  1 ,  Susanne Hafner  2 ,  Sophia Lang  2 ,  Michael Schmiech  2 ,  Tatiana Syrovets  2 ,  Thomas Simmet  2
Affiliations
  • 1. Department of Pharmacognosy, College of Pharmacy, Cairo University , Giza 11562, Egypt.
  • 2. Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University , Ulm D-89081, Germany.
  • 3. Pharmacognosy Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA) , Cairo 11562, Egypt.
PMID: 29190084 DOI: 10.1021/acs.jnatprod.7b00546
Abstract

We investigated the cytotoxic potential of the cardenolide glycoside acovenoside A against non-small-cell lung Cancer cells. Lung Cancer is the leading cause of cancer-related mortality and the second most common Cancer diagnosed. Epidemiological studies revealed a direct correlation between the regular administration of cardiac glycosides and a lower incidence of various cancers. Acovenoside A, isolated from the pericarps of Acokanthera oppositifolia, potently inhibited proliferation and induced cytotoxicity in A549 non-small-cell lung Cancer cells with an IC50 of 68 ± 3 nM after 48 h of exposure. Compared to the antineoplastic agent doxorubicin, acovenoside A was more potent in inhibiting the viability of A549 Cancer cells. Moreover, acovenoside A exhibited selectivity against Cancer cells, being significantly less toxic to lung fibroblasts and nontoxic for peripheral blood mononuclear cells. Analysis of the cell cycle profile in acovenoside A-treated A549 cells revealed mitotic arrest, due to accumulation of the G2/M regulators cyclin B1 and CDK1, and cytokinesis failure. Furthermore, acovenoside A affected the mitochondrial membrane integrity and induced production of radical oxygen species, which resulted in induction of canonical Apoptosis, manifested by Caspase 3 activation and DNA fragmentation. Based on our results, acovenoside A warrants further exploration as a potential Anticancer lead.