3,3′,5,5′-tetramethoxybiphenyl-4,4′diol induces cell cycle arrest in G2/M phase and apoptosis in human non-small cell lung cancer A549 cells

Abstract

Lung cancer is one of the leading causes of cancer-related death worldwide. It has aggressive manifestation, high ability to promote metastasis and late diagnosis. In the present study, we investigated the cytotoxic effect of 3,3′,5,5′-tetramethoxybiphenyl-4,4′diol (TMBP), against the A549 human non-small cell lung carcinoma lineage. The A549 cell line was treated for 72h with TMBP (12.5–200 μM) with and subsequently defined the 50% inhibitory concentration (148 μM ± 0.05), from which tests were performed to determine the viability, volume, and regulation of the cell cycle. Finally, we investigated the death mechanisms involved in the action of the treatments by flow cytometry and fluorimetry. The TMBP-treatment of primary cells, peritoneal macrophages, and sheep erythrocytes did not reduce the viability of these cells. On the other hand, TMBP was able to reduce the viability of the investigated cell line, by cytotoxic action and to promote the reduction of cell size. Subsequently, we found that TMBP treatment was able to increase the production of reactive oxygen species, cause mitochondrial depolarization, induce cell cycle arrest in G2/M phase and lead to death by direct apoptosis. Thus, this study revealed that TMBP could be a promising candidate for the development of antitumor drugs targeting lung cancer.