Erianthridin Induces Non-small Cell Lung Cancer Cell Apoptosis through the Suppression of Extracellular Signal-regulated Kinase Activity

Abstract

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.

Consensus Virtual Screening Protocol Towards the Identification of Small Molecules Interacting with the Colchicine Binding Site of the Tubulin‐microtubule System

“…Three ( 1 – 3 ) of the five selected compounds have shown inhibitory activity against different cancer cell lines. Thus, 5‐[2‐(4‐hydroxy‐3‐methoxyphenyl)ethyl]‐2,3‐dimethoxyphenol ( 1 ) (Figure 3 ), identified as FQNP278 in Table S1 in the Supporting Information, exhibits cytotoxic activity against the HL60 (IC 50 : 24 μM) and MCF7 (IC 50 : 27 μM) cell lines, [24] 9,10‐dihydro‐3,4‐dimethoxy‐2,7‐phenanthrenediol or erianthridin ( 2 ), identified as FQNP280 in Table S1, exhibits cytotoxic activity against the HL60 (IC 50 : 44 μM), H460 (IC 50 : 150 μM), A549 (IC 50 : 161 μM) cell lines,[ 25 , 26 ] 2‐(3,4‐dimethoxyphenyl)‐5,7‐dihydroxy‐6‐methoxy‐4 H ‐1‐benzopyran‐4‐one ( 3 ), identified as FQNP112 in Table S1, shows cytotoxic activity against the MKN1 (IC 50 : 50 μM), SNU601 (IC 50 : 50 μM), and MCF7 (IC 50 : 90 μM) cell lines as well as cytostatic activity against NCI‐60 (GI 50 : 15 μM) cell line. [ 27 , 28 ] Additionally, compound 3 has been tested on tubulin polymerization assays showing inhibitory activity (IC 50 :>40 μM).…”

Comprehensive review of Bcl‐2 family proteins in cancer apoptosis: Therapeutic strategies and promising updates of natural bioactive compounds and small molecules

“…Erianthridin is a natural phenanthrene compound that has demonstrated potential as a natural anticancer agent, particularly against non-small cell lung cancer (Boonjing et al, 2021;Pothongsrisit et al, 2021). Erianthridin treatment led to a significant reduction in…”

“…Erianthridin is a natural phenanthrene compound that has demonstrated potential as a natural anticancer agent, particularly against non‐small cell lung cancer (Boonjing et al, 2021; Pothongsrisit et al, 2021). Erianthridin treatment led to a significant reduction in the viability of both H460 and A549 cells, with IC 50 values ranging from 150 to 162 μM, and the induction of apoptotic cell death.…”

Targeting the PI3K/AKT/mTOR Signaling Pathway in Lung Cancer: An Update Regarding Potential Drugs and Natural Products

“…Likewise, erianthridin is a phenanthrene derived from Dendrobium formosum that was recently reported to have potent antimetastatic and cytotoxic effects on lung cancer [ 96 , 221 ]. Erianthridin suppresses the metastatic behavior of A549 and H460 lung cancer cells through the AKT/mTOR pathway.…”

“…Furthermore, an in vivo metastasis model confirmed the strong suppressive effect of this compound on lung colonization. Interestingly, erianthridin was not toxic to normal lung and tubular epithelial cells, whereas cytotoxicity was often observed in response to cisplatin, a standard therapy for lung cancer [ 221 ]. Overall, phenanthrene derivatives are strong AKT inhibitors, suggesting that they might serve as prototype compounds for further anti-lung cancer research and development.…”