7,8-Dihydroxy-4-methylcoumarin induces apoptosis of human lung adenocarcinoma cells by ROS-independent mitochondrial pathway through partial inhibition of ERK/MAPK signaling.
Coumarins have attracted intense interest in recent years because they have been identified from natural sources, especially green plants and have diverse pharmacological properties. In this study, we investigated whether 7,8-dihydroxy-4-methylcoumarin (DHMC) caused apoptosis in A549 human non-small cell lung carcinoma cells (NSCLC) and, if so, by what mechanisms. Here, we show that, in A549 human NSCLC cells, DHMC induces apoptosis through mitochondria-mediated caspase-dependent pathway. Although an increase in the levels of reactive oxygen species (ROS) was observed, pre-treatment with antioxidant showed no protective effect against DHMC-induced apoptosis. In addition, our immunoblot data revealed that DHMC treatment led to down-regulation of Bcl-xl, Bax, p21, Cox-2, p53 and upregulation of c-Myc. Results in the present study for the first time suggest that DHMC induces apoptosis in human lung A549 cells through partial inhibition of ERK/MAPK signaling.
Goel
Anita
A
Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Mall Road, Delhi 110 007, India.
Prasad
Ashok K
AK
Parmar
Virinder S
VS
Ghosh
Balaram
B
Saini
Neeru
N
D000230:Adenocarcinoma; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003374:Coumarins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms; D048370:MAP Kinase Kinase 2 / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
C114368:7,8-dihydroxy-4-methylcoumarin; D003374:Coumarins; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D048370:MAP Kinase Kinase 2