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. (1st August 2020)

• Record Type: Journal Article
• Authors: Concato, Virginia Marcia; Tomiotto-Pellissier, Fernanda; Silva, Taylon Felipe; Gonçalves, Manoela Daiele; Bortoleti, Bruna Taciane da Silva; Detoni, Mariana Barbosa; Siqueira, Elaine da Silva; Rodrigues, Ana Carolina Jacob; Schirmann, Jéseka Gabriela; Barbosa-Dekker, Aneli de Melo; Costa, Idessania Nazareth; Conchon-Costa, Ivete; Miranda-Sapla, Milena Menegazzo; Mantovani, Mario Sergio; Pavanelli, Wander Rogério
• Is Part Of: Chemico-biological interactions. Volume 326(2020)
• Publication Date: 2020-08-01
• Subjects: Lung cancer -- Cytotoxic -- Cell cycle -- Reactive oxygen species -- Apoptosis; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2020.109133
• Languages: English
• ISSNs: 0009-2797

Abstract

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. Graphical abstract: A schematic model of the cytotoxic action of TMBP on A549 cell line. TMBP treatment leads to the reduction of A549 cell line proliferation by induction of cytotoxicity, can cause morphological changes, with cell size reduction. In addition, the IC50 treatment of TMBP was able to generate reactive oxygen species (ROS), promote mitochondrial depolarization, arrest the cell cycle in G2/M phases, and induce cell death by late-apoptosis process. Image 1 Highlights: In silico predictions showed good drug-likeness potential for TMBP. TMBP promotes cytotoxic action and changes in cell size in A549 cells. TMBP increases the production of ROS and disrupts the cell cycle in G2/M. TMBP alters the ΔΨm and. promotes formation of droplets lipid in A549. Treatment with TMBP induces apoptosis in tumor cells.