Acovenoside A Induces Mitotic Catastrophe Followed by Apoptosis in Non-Small-Cell Lung Cancer Cells
El Gaafary M.; Ezzat, Shahira M; El Sayed A.M.; Sabry O.M.; Hafner S.; Lang S.; Schmiech M.; Syrovets T.; Simmet T.
Date issued:
2017
Publisher:
American Chemical Society
Series Info:
Journal of Natural Products
80
Type:
Article
Keywords:
October University for Modern Sciences and Arts
,
جامعة أكتوبر للعلوم الحديثة والآداب
,
University of Modern Sciences and Arts
,
MSA University
,
acovenoside a
,
cardenolide
,
caspase 3
,
cyclin B1
,
cyclin dependent kinase 1
,
cytotoxic agent
,
doxorubicin
,
ebselen
,
norphenazone
,
protein p53
,
reactive oxygen metabolite
,
tempol
,
unclassified drug
,
acovenoside A
,
antineoplastic agent
,
cardenolide
,
doxorubicin
,
reactive oxygen metabolite
,
Acokanthera oppositifolia
,
apoptosis
,
Article
,
cell cycle
,
cell cycle progression
,
cell proliferation
,
cell viability
,
controlled study
,
cytokinesis
,
cytotoxicity
,
DNA fragmentation
,
drug mechanism
,
drug sensitivity
,
fluorescence
,
G2 phase cell cycle checkpoint
,
human
,
human cell
,
IC50
,
lung fibroblast
,
lung non-small cell carcinoma cell line
,
M phase cell cycle checkpoint
,
mitochondrial membrane potential
,
mitosis
,
mitosis inhibition
,
non small cell lung cancer
,
oxidative stress
,
pericarp
,
peripheral blood mononuclear cell
,
protein phosphorylation
,
shrub
,
A-549 cell line
,
apoptosis
,
cell survival
,
drug effect
,
epidemiology
,
fibroblast
,
lung tumor
,
metabolism
,
mitochondrial membrane
,
mitosis
,
mononuclear cell
,
non small cell lung cancer
,
tumor cell line
,
A549 Cells
,
Antineoplastic Agents
,
Apoptosis
,
Carcinoma, Non-Small-Cell Lung
,
Cardenolides
,
Cell Line, Tumor
,
Cell Proliferation
,
Cell Survival
,
DNA Fragmentation
,
Doxorubicin
,
Epidemiologic Studies
,
Fibroblasts
,
G2 Phase Cell Cycle Checkpoints
,
Humans
,
Leukocytes, Mononuclear
,
Lung Neoplasms
,
Mitochondrial Membranes
,
Mitosis
,
Reactive Oxygen Species
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 IC 50 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 G 2 /M regulators cyclin B 1 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. � 2017 The American Chemical Society and American Society of Pharmacognosy.
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