(−)-Hinokinin Induces G2/M Arrest and Contributes to the Antiproliferative Effects of Doxorubicin in Breast Cancer Cells

Nayanne Larissa Cunha; Gabriella Machado Teixeira; Thomás Duzzi Martins; Anderson Roberto Souza; Pollyana Francieli Oliveira; Guilherme Venâncio Símaro; Karen Cristina Souza Rezende; Natália dos Santos Gonçalves; Daniel Gottardo Souza; Denise Crispim Tavares; Marcio Luís Andrade Silva; Raquel Alves dos Santos

doi:10.1055/s-0042-101761

Planta Medica, Table of Contents

Planta Med 2016; 82(06): 530-538
DOI: 10.1055/s-0042-101761

Biological and Pharmacological Activity

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

(−)-Hinokinin Induces G2/M Arrest and Contributes to the Antiproliferative Effects of Doxorubicin in Breast Cancer Cells

Authors

Nayanne Larissa Cunha

University of Franca, Franca, SP, Brazil
Gabriella Machado Teixeira

University of Franca, Franca, SP, Brazil
Thomás Duzzi Martins

University of Franca, Franca, SP, Brazil
Anderson Roberto Souza

University of Franca, Franca, SP, Brazil
Pollyana Francieli Oliveira

University of Franca, Franca, SP, Brazil
Guilherme Venâncio Símaro

University of Franca, Franca, SP, Brazil
Karen Cristina Souza Rezende

University of Franca, Franca, SP, Brazil
Natália dos Santos Gonçalves

University of Franca, Franca, SP, Brazil
Daniel Gottardo Souza

University of Franca, Franca, SP, Brazil
Denise Crispim Tavares

University of Franca, Franca, SP, Brazil
Marcio Luís Andrade Silva

University of Franca, Franca, SP, Brazil
Raquel Alves dos Santos

University of Franca, Franca, SP, Brazil

Abstract

Breast cancer incidence rises worldwide and new chemotherapeutical strategies have been investigated to overcome chemoresistance. (−)-Hinokinin is a dibenzylbutyrolactone lignan derived from the partial synthesis of (−)-cubebin extracted from Piper cubeba seeds. Biological effects of dibenzylbutyrolactone lignans include antiviral, antitumor, anti-inflammatory, and trypanocidal activities. In the present study, we evaluated the ability of (−)-hinokinin to modulate the antiproliferative effects of doxorubicin intumoral (MCF-7 and SKBR-3) and normal (MCF-10 A) breast cell lines. Treatment with (−)-hinokinin did not affect the cellular proliferation or contribute to the antitproliferative effects of doxorubicin in MCF-10 A cells. After 24 and 48 hours of treatment with (−)-hinokinin, MCF-7 and SKBR-3 were accumulated in G2/M and, when combined with doxorubicin, (−)-hinokinin contributed to the antiproliferative effects of this chemotherapic by modulation of the cyclin-dependent kinase inhibitor 1. Apoptotic cell death was observed in response to (−)-hinokinin alone in MCF-7, but not in SKBR-3 even 72 hours after treatment. In MCF-7, doxorubicin-induced apoptosis was not increased by (−)-hinokinin. The findings of the present study suggest (−)-hinokinin as an antiproliferative agent that contributes to the effects of doxorubicin. (−)-Hinokinin modulates apoptotic cell death via the molecular regulation of the cell cycle and apoptotic control genes, but the cellular genetic background directly affects the cell fate decision in response to treatment.

Key words

(−)-hinokinin - breast cancer - cell proliferation - cell death - cell cycle

Full Text

References

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