ABSTRACT
Medium-chain fatty acids (MCFAs) have 6-12 carbon atoms and are instantly absorbed into the bloodstream before traveling to the portal vein and the liver, where they are immediately used for energy and may have antitumor effects. Its role in breast cancer is poorly understood. To investigate the apoptosis-inducing effect of MCFAs in breast cancer cells, cell viability assay, colony formation assay, cell migration assay, cell invasion assay, nuclear morphology, cell cycle assay, intracellular reactive oxygen species (ROS), matrix metalloproteinase (MMP), apoptosis, RT-qPCR analysis, and Western blot analysis were performed. In the present study, MCFA treatments reduced proliferative capability, increased ROS level, increased the depletion of MMP, induced G0/G1 and S phase cell cycle arrest, and late apoptosis of breast cancer cells in an effective concentration. Besides, MCFA treatment contributed to the upregulation of proapoptotic protein (BAK) and caspase-3, and the downregulation of antiapoptotic protein (Bcl-2). Mechanistically, phosphorylation levels of EGFR, Akt, and mTOR were significantly reduced in breast cancer cells treated with MCFAs. However, no significant changes in apoptosis and signaling-related proteins were observed in lauric acid-treated ER-positive cancer cells. Our findings suggested that MCFAs suppressed breast cancer cell proliferation by modulating the PI3K/Akt/mTOR signaling pathway. MCFAs may be a promising therapeutic drug for treating breast cancer.
Subject(s)
Apoptosis , Breast Neoplasms , Cell Proliferation , Fatty Acids , Proto-Oncogene Proteins c-bcl-2 , Signal Transduction , Female , Humans , Apoptosis/drug effects , Breast Neoplasms/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Fatty Acids/metabolism , Fatty Acids/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , MCF-7 Cells , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , TOR Serine-Threonine Kinases/metabolismABSTRACT
Tongue cancer is distinguished by aggressive behavior, a high risk of recurrence, lymph, and distant metastases. Hypoxia-Induced Factor 1 α functions as a CD9 transcription factor. CD9 is a transmembrane protein that may be found on the cell membrane. It can modulate the expression of the Epidermal Growth Factor Receptor (EGFR) pathway. ELISA was used to measure serum CD9, p-EGFR, and p-Akt levels in 70 tongue cancer patients and 35 healthy controls. RT-PCR was used to analyze the gene expression of the related genes. The gene as well as protein expression of CD9, EGFR/p-EGFR, and Akt/p-Akt was significantly higher in case subjects when compared with the controls. The expression of CD9 was higher in case subjects who were smokers/alcoholics when to control subjects who were smokers/alcoholics. Overexpression of CD9 due to hypoxic conditions leads to the activation of EGFR-signaling pathway resulting in cancer progression, resistance to chemotherapy. Hence, CD9 could be a potential target to suppress cancer progression.
