Inorganic Phosphate Prevents Erk1/2 and Stat3 Activation and Improves Sensitivity to Doxorubicin of MDA-MB-231 Breast Cancer Cells

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Luigi SapioSilvio Naviglio

Abstract

Due to its expression profile, triple-negative breast cancer (TNBC) is refractory to the most effective targeted therapies available for breast cancer treatment. Thus, cytotoxic chemotherapy represents the mainstay of treatment for early and metastatic TNBC. Therefore, it would be greatly beneficial to develop therapeutic approaches that cause TNBC cells to increase their sensitivity to cytotoxic drugs. Inorganic phosphate (Pi) is emerging as an important signaling molecule in many cell types. Interestingly, it has been shown that Pi greatly enhances the sensitivity of human osteosarcoma cell line (U2OS) to doxorubicin. We investigated the effects of Pi on the sensitivity of TNBC cells to doxorubicin and the underlying molecular mechanisms, carrying out flow cytometry-based assays of cell-cycle progression and cell death, MTT assays, direct cell number counting and immunoblotting experiments. We report that Pi inhibits the proliferation of triple-negative MDA-MB-231 breast cancer cells mainly by slowing down cell cycle progression. Interestingly, we found that Pi strongly increases doxorubicin-induced cytotoxicity in MDA-MB-231 cells by apoptosis induction, as revealed by a marked increase of sub-G1 population, Bcl-2 downregula...Continue Reading

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Citations

Jun 21, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yao WeiLimin Li
Mar 30, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ji YangYunmei Yang
Dec 15, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Sumei ZhouXiaohua Zhang
Sep 28, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Michelina CatauroSilvio Naviglio
Jun 28, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Di ChenYue Yin
Nov 29, 2017·Oxidative Medicine and Cellular Longevity·Donato CappettaKonrad Urbanek

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Methods Mentioned

BETA
FACS
enzyme-linked immunosorbent assay
Flow

Software Mentioned

ImageJ
ModiFIT Cell Cycle Analysis

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