Autophagic genes and antioxidant status during doxorubicin therapy under temperature-stressed conditions in breast cancer cells

Abstract

ObjectivesAutophagy as a cellular event swings between apoptosis induction and cellular maintenance during chemotherapy. The interplay between autophagy and reactive oxygen species (ROS) remains obscure in cancer progression and treatment. This study aimed to determine the combination effect of chemotherapy and hyperthermia on cancer cell proliferation, autophagy signaling, and oxidative stress status. MethodsTo estimate the autophagic genes' role and antioxidant capacity involvement during chemotherapy, human breast cancer cell lines (MCF7 and CAL51) were exposed to a high temperature at 42 °C and treated with doxorubicin (DOX). The MTT assays were performed to determine the cell survival levels, and the autophagic gene expression levels (ATG5, LC3A, LC3B, and Beclin1) were analyzed. The intracellular TAS (total antioxidant status) and SOD (superoxide dismutase) activities were determined. ResultsThe combined effects of high temperature with chemotherapy significantly reduced cell viability and cell survival compared to cells treated with the chemotherapeutic agent DOX alone. The cell's autophagic gene activities were significantly increased after exposure to 42 °C temperature and DOX-based chemotherapy compared to the cells treated with DOX alone. It was observed that TAS and SOD activities were increased in the cell lines exposed to high temperatures with DOX compared to the cells treated with DOX alone. Increased autophagic gene expression levels and cell death were observed in response to the high temperature and DOX treatment in breast cancer cells. ConclusionThe study may provide a plausible route and treatment plan for the individual adoption of cancer chemotherapy and be developed as part of the personalized medicine protocol.