Mychonastes sp. 247 Induces Apoptosis of A549 Human Lung Cancer Cells by Promoting STRA6-Mediated Reactive Oxygen Species Production

Abstract

Mychonastes sp. 247 is a newly isolated freshwater microalga. Mychonastes sp. 247 methanolic extract (ME) suppresses the growth of A549 human non-small-cell lung cancer (NSCLC) cells. However, the underlying mechanism of this anticancer effect remains unclear. The present study aimed to reveal the underlying mechanism of the anticancer effect of ME in A549 cells. The components of ME, their cytotoxicity in normal cells, and their inhibitory effect on the growth and migration of two-dimensional and three-dimensional cultured cancer cells were investigated. We also showed that ME upregulated the mRNA levels of signaling receptors and transporters of retinol (STRA6) and cytochrome P450 family 26 subfamily B member 1, and increased the protein expression of phosphorylated c-Jun N-terminal kinase, B-cell lymphoma protein 2/(Bcl-2)-associated X (Bcl-2/Bax), and cleaved caspase-3. Moreover, co-treatment with N-acetyl-L-cysteine reversed the ME-induced changes in the levels of STRA6 and reactive oxygen species (ROS), confirming their role in the ME-mediated anticancer effect. To the best of our knowledge, this is the first study elucidating the pathway by which ME induces anticancer effects in lung cancer cells. Our results reveal that ME induces NSCLC apoptosis by regulating ROS levels via the STRA6 pathway, suggesting ME as a prospective anticancer agent for lung cancer treatment.