Gallic acid sensitizes paclitaxel-resistant human ovarian carcinoma cells through an increase in reactive oxygen 
species and subsequent downregulation of ERK activation

Sánchez-Carranza,Jessica  Nayelli; Díaz,J.  Fernando; Redondo-Horcajo,Mariano; Barasoain,Isabel; Alvarez,Laura; Lastres,Pedro; Romero-Estrada,Antonio; Aller,Patricio; González-Maya,Leticia

doi:10.3892/or.2018.6382

Gallic acid sensitizes paclitaxel-resistant human ovarian carcinoma cells through an increase in reactive oxygen species and subsequent downregulation of ERK activation

Authors:
- Jessica Nayelli Sánchez-Carranza
- J. Fernando Díaz
- Mariano Redondo-Horcajo
- Isabel Barasoain
- Laura Alvarez
- Pedro Lastres
- Antonio Romero-Estrada
- Patricio Aller
- Leticia González-Maya
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Affiliations: Faculty of Pharmacy, Autonomous University of Morelos State (UAEM), Cuernavaca, Morelos 62209, México, Biological Research Center (CIB), Spanish National Research Council - CSIC, 28040 Madrid, Spain, The Center of Chemical Research (CIQ)-IICBA, Autonomous University of Morelos State (UAEM), Cuernavaca, Morelos 62209, México
Published online on: April 18, 2018 https://doi.org/10.3892/or.2018.6382
Pages: 3007-3014

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Abstract

Paclitaxel (PTX) is currently used as a front-line chemotherapeutic agent for several types of cancer, including ovarian carcinoma; however, PTX-resistance frequently arises through multiple mechanisms. The development of new strategies using natural compounds and PTX in combination has been the aim of several prior studies, in order to enhance the efficacy of chemotherapy. In this study, we found the following: (i) gallic acid (GA), a phenolic compound, potentiated the capacity of PTX to decrease proliferation and to cause G2/M cycle arrest in the PTX-resistant A2780AD ovarian cancer cell line; (ii) GA exerted a pro-oxidant action by increasing the production of reactive oxygen species (ROS), and co-treatment with the antioxidant agent N‑acetyl-L‑cysteine (NAC) prevented GA+PTX-induced cell proliferation inhibition and G2/M phase arrest; (iii) PTX stimulated ERK phosphorylation/activation, and co-treatment with the MEK/ERK inhibitor PD98049 potentiated the proliferation inhibition and G2/M phase arrest; (iv) and finally, GA abrogated the PTX-induced stimulation of ERK phosphorylation, a response that was prevented by co-treatment with NAC. Taken together, these results indicate that GA sensitizes PTX-resistant ovarian carcinoma cells via the ROS‑mediated inactivation of ERK, and suggest that GA could represent a useful co-adjuvant to PTX in ovarian carcinoma treatment.

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