Streptomyces-derived natural products have been become a major focus of anti-
tumor drug discovery studies.
Neoantimycin F (
NAT-F), was isolated from Streptomyces conglobatus by our group. Here, we examined the anti-
cancer activities and its underlying molecular mechanisms implicated in
NAT-F-induced apoptosis of
non-small cell lung cancer (NSCLC) cells. Our results showed that
NAT-F exerted excellent growth-inhibitory activity against PC9 and H1299 cells in a concentration-dependent manner.
NAT-F-induced cell cycle arrest at S and G0/G1 phase in PC9 and H1299 cells, respectively. Further investigation revealed that the key
proteins (including cyclinD1, cyclinE1, cyclinB1, CDK2, and CDK4) were involved in the cell regulation by
NAT-F. Additionally,
NAT-F significantly increased the production of
reactive oxygen species (ROS), induced DNA damage, nuclear condensation, and cell apoptosis in both cell lines. Moreover, loss of the mitochondrial membrane potential (
MMP) was markedly induced by
NAT-F. Additional results revealed that
NAT-F could up-regulate
pro-apoptotic protein Bax and down-regulate
anti-apoptotic protein Bcl-2, Mcl-1, and Bcl-xL, resulting in
cytochrome c release from mitochondria and sequential activation of
caspase-9 and -3, as well as the cleavage of
poly (ADP-ribose) polymerase. Meanwhile,
c-Jun N-terminal kinase (JNK),
p38 MAPK (p38), and
extracellular signal-regulated kinase (ERK) signaling pathway were also involved in anti-
cancer activity of
NAT-F in NSCLC cells. Taken together, these findings indicated that
NAT-F possessed anti-proliferative effect and induced apoptosis in NSCLC cells in vitro and may be conducive to promote the development of novel anti-NSCLC agents.