GSE178508
Antitumor Effects of 3-bromoascochlorin on Small Cell Lung Cancer via Inhibiting MAPK Pathway
Small cell lung cancer (SCLC) was defined as a recalcitrant cancer, and novel therapies are urgently needed. Marine natural products (MNP) may bring continuing hope for treatment of SCLC. In this study, 3-bromoascochlorin (BAS), an MNP isolated from the coral-derived fungus Acremonium sclerotigenum GXIMD 02501, was primarily screened out with antiproliferative activity towards SCLC cell lines. Then Western blotting (WB) and flow cytometry were conducted, and we found BAS could induce the apoptosis of H446 and H69AR cells. Besides, BAS could suppress the invasion and migration of H446. In a SCLC xenograft mice model, BAS inhibited the growth of tumor without affecting the body weight of mice. Finally, the underlying mechanisms were preliminarily explored. According to the results of RNA-seq, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and WB, we draw the conclusion that BAS exerted antitumor activity via inhibiting mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK) pathway. In short, we discovered an MNP as a potential drug lead against SCLC. Overall design: H446 cells were treated with vehicle or the small molecule BAS (5 µM) and BAS (10 µM), for 48 h before RNA extraction. RNA-seq libraries were from 1 µg total RNA which was extracted using the total RNA isolation kit (Tiangen, BJ, China) and reverse transcribed with reverse transcriptase M-MLV (Takara, DL, China), according to the manufacturer's instructions. Libraries were validated with an Agilent 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA).