Due to the high mortality of lung cancer, natural derivative compounds have been promoted
as versatile sources for anticancer drug discovery. Erianthridin, a phenanthrene compound
isolated from Dendrobium formosum, exhibits intriguing apoptosis-inducing effects in non-small cell lung cancer cells.
Apoptotic nuclei staining assays showed that apoptotic cells with DNA fragmentation
and apoptotic bodies were apparent, and an increase in annexin V-FITC-positive cells
were found in cells treated with erianthridin. The apoptosis protein markers for cleaved
caspase-3 and cleaved poly-ADP-ribose polymerase were significantly upregulated in
response to erianthridin. A mechanistic investigation revealed that erianthridin was
able to attenuate extracellular signal-regulated kinase activity and thereby mediate
apoptosis through the modulation of Bcl-2 family protein levels. U0126, an extracellular
signal-regulated kinase inhibitor, augmented the apoptosis-inducing effect of
erianthridin; in contrast, overexpression of exogenous extracellular signal-regulated
kinase substantially abrogated erianthridin activity. Furthermore, an in vitro 3D tumorigenesis assay showed that erianthridin was able to potentially suppress
lung cancer cell proliferation. This study is the first to report a promising cytotoxic
effect of erianthridin, which provides preclinical evidence for further research and
development of this compound.
Key words
apoptosis - Bcl-2 family proteins -
Dendrobium densiflorum
- erianthridin - extracellular signal-regulated kinase - Orchidaceae - non-small cell
lung cancer cells