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

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

Volume: 14 Issue: 8

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:

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

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.

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Gasparotto Juciano, Somensi Nauana, Kunzler Alice, Girardi Saibro Carolina, Pasquali Augusto de Bittencourt Matheus, Ramos Miranda Vitor, Simoes-Pires Andre, Quintans-Junior Jose Lucindo, Branco Alexsandro, Moreira Claudio Fonseca Jose and Gelain Pens Daniel, Hecogenin Acetate Inhibits Reactive Oxygen Species Production and Induces Cell Cycle Arrest and Senescence in the A549 Human Lung Cancer Cell Line, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (8) . https://dx.doi.org/10.2174/1871520614666140408151751