Hecogenin Acetate Inhibits Reactive Oxygen Species Production and Induces Cell Cycle Arrest and Senescence in the A549 Human Lung Cancer Cell Line

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 14, 10 Issues, 2014


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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  • 85th of 202 in Oncology

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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Hecogenin Acetate Inhibits Reactive Oxygen Species Production and Induces Cell Cycle Arrest and Senescence in the A549 Human Lung Cancer Cell Line

Author(s): Juciano Gasparotto, Nauana Somensi, Alice Kunzler, Carolina Saibro Girardi, Matheus Augusto de Bittencourt Pasquali, Vitor Miranda Ramos, Andre Simoes-Pires, Lucindo Jose Quintans-Junior, Alexsandro Branco, Jose Claudio Fonseca Moreira and Daniel Pens Gelain

Affiliation: Street Address: Rua Ramiro Barcelos, 2600 – anexo, CEP 90035-003, Porto Alegre, RS, Brazil.

Abstract

Cellular and molecular mechanisms related to lung cancer have been extensively studied in recent years, but the availability of effective treatments is still scarce. Hecogenin acetate, a natural saponin presenting a wide spectrum of reported pharmacological activities, has been previously evaluated for its anticancer/antiproliferative activity in some in vivo and in vitro models. Here, we investigated the effects of hecogenin acetate in a human lung cancer cell line. A549 non-small lung cancer cells were exposed to different concentrations of hecogenin acetate and reactive species production, ERK1/2 activation, matrix metalloproteinase expression, cell cycle arrest and cell senescence parameters were evaluated. Hecogenin acetate significantly inhibited increase in intracellular reactive species production induced by H2O2. In addition, hecogenin acetate blocked ERK1/2 phosphorylation and inhibited the increase in MMP-2 caused by H2O2. Treatment with hecogenin acetate induced G0/G1-phase arrest at two concentrations (75 and 100 µM, 74% and 84.3% respectively), and increased the staining of senescence-associated β -galactosidase positive cells. These data indicate that hecogenin acetate is able to exert anti-cancer effects by modulating reactive species production, inducing cell cycle arrest and senescence and also modulating ERK1/2 phosphorylation and MMP-2 production.




Keywords: Cell cycle, ERK1/2, hecogenin acetate, non-small cell lung cancer, senescence.

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Article Details

Volume: 14
Issue Number: 8
First Page: 1128
Last Page: 1135
Page Count: 8
DOI: 10.2174/1871520614666140408151751
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