N-(2-hydroxyphenyl)-2-phenazinamine from Nocardiopsis exhalans induces p53-mediated intrinsic apoptosis signaling in lung cancer cell lines.

ABSTRACT

The present study aims to investigate the effect and the molecular mechanism of N-(2-hydroxyphenyl)-2-phenazinamine (NHP) isolated from Nocardiopsis exhalans against the proliferation of human lung cancer cells. The cytotoxic activity of NHP against A549 and H520 cells was determined using MTT assay. The cytotoxic activity of NHP against A549 and H520 lung cancer cells showed excellent activity at 75 µg/mL and damage the mitochondrial membrane and nucleus by generating oxidative stress. NHP causes nuclear condensation and induces apoptosis which was confirmed using AO/EB and PI/DAPI dual staining assay. Moreover, the NHP downregulates the oncogenic genes such as IL-8, TNFα, MMPs and BcL2 and also upregulates the expression of apoptosis marker genes such as Cyto C, p53, p21, caspase 9/3 in A549 and H520 human lung cancer cells. Considering the strong anticancer activity of NHP against lung cancer, NHP may be further evaluated as a potential anticancer drug for the treatment of lung cancer.