Synergistic Tumoricidal Effects of Alpha-Lipoic Acid and Radiotherapy on Human Breast Cancer Cells via HMGB1

Abstract

Purpose Radiotherapy (RT) is one of main strategies of cancer treatment. However, some cancer cells are resistant to radiation-induced cell death, including apoptosis. Therefore, alternative approaches targeting different anti-tumor mechanisms such as cell senescence are required. This study aimed to investigate the synergistic effect of alpha-lipoic acid (ALA) on radiation-induced cell death and senescence in MDA-MB-231 human breast cancer cells.Materials and Methods The cells were divided into four groups depending on the cell treatment (control, ALA, RT, and ALA+RT). Cells were analyzed for morphology, apoptotic cell death, mitochondrial reactive oxygen species, membrane potential, cellular senescence, and cell cycle.Results Our data showed that ALA significantly promoted apoptotic cell death when combined with RT, as reflected by Annexin V staining, expression of apoptosis-related factors, mitochondrial damages as well as cell morphological changes and reduction of cell numbers. In addition, ALA significantly enhanced radiation-induced cellular senescence, which was shown by increased HMGB1 expression in the cytosol fraction compared to the control, increased p53 expression compared to the control, activation of p38 as well as nuclear factor кB, and G2/M cell cycle arrest.Conclusion The current study is the first report showing a new mode of action (senescence induction) of ALA beyond apoptotic cell death in MDA-MB-231 cancer cells known to be resistant to RT.

Anticancer Effect of Benzimidazole Derivatives, Especially Mebendazole, on Triple-Negative Breast Cancer (TNBC) and Radiotherapy-Resistant TNBC In Vivo and In Vitro

“…In addition to timesaving and cost reduction, drug repurposing has a significant advantage in ensuring safety through well-known pharmacokinetic and pharmacodynamic features. In the field of oncology, with the advent of metformin, immunotherapy, and alpha-lipoic acid, interest is increasing in drug repurposing of non-anticancer drugs to anticancer drugs [ 9 , 10 ].…”

The potential health benefits of aloin from genus Aloe

“…High mobility group protein B1 (HMGB1) is a highly conserved nuclear DNA‐binding protein related to a variety of cancer types, and its high expression is closely associated with tumor cell apoptosis, proliferation, and migration (Choi et al, 2021). Tao et al (2019) incubated human gastric cancer HGC‐27 cells with aloin for 24 hr and observed that cell viability was significantly decreased and morphological changes in apoptosis appeared in the nucleus under the influence of aloin.…”

“…High mobility group protein B1 (HMGB1) is a highly conserved nuclear DNA-binding protein related to a variety of cancer types, and its high expression is closely associated with tumor cell apoptosis, proliferation, and migration (Choi et al, 2021). and invasion potential.…”

Drug Repositioning and Subgroup Discovery for Precision Medicine Implementation in Triple Negative Breast Cancer

“…It downregulates furin, which, in turn, inhibits the maturation of IGF-1R [ 101 , 102 ]. Combining lipoic acid with radiation therapy was found to overcome the resistance to radiation therapy and promote apoptosis [ 103 ].…”