Cordycepin Induces Apoptosis and Inhibits Proliferation of Human Lung Cancer Cell Line H1975 via Inhibiting the Phosphorylation of EGFR

Abstract

Abstract:Cordycepin is an active component of the traditional Chinese medicine Cordyceps sinensis and Cordyceps militaris with notable anticancer activity. Though the prominent inhibitory activity was reported in different kinds of cancer cell lines, the concrete mechanisms remain elusive. It was reported that cordycepin could be converted into tri-phosphates in vivo to confuse a number of enzymes and interfere the normal cell function. For the inhibitory mechanism of EGFR inhibitors and the structure similarity of ATP and tri-phosphated cordycepin, human lung cancer cell line H1975 was employed to investigate the inhibitory effect of cordycepin. The results showed that cordycepin could inhibit cell proliferation and induce apoptosis in a dose-dependent manner. Cell cycle analysis revealed that H1975 cells could be arrested at the G 0 /G 1 phase after cordycepin treatment. The expression levels of apoptosis-related protein Caspase-3 and Bcl-2 and phosphorylated expression levels of EGFR, AKT and ERK1/2 were all decreased compared with the control group stimulated with EGF. However, the protein expression levels of proapoptotic protein Bax and cleaved caspase-3 were increased. These results implied that cordycepin could inhibit cell proliferation and induce apoptosis via the EGFR signaling pathway. Our results indicated that there was potential to seek a novel EGFR inhibitor from cordycepin and its chemical derivatives.

Design, synthesis and biological evaluation of valepotriate derivatives as novel antitumor agents

“…As recently reported, several plants-derived compounds possessed anti-proliferation activity against H1975, and the IC 50 value varied from 3 to 15 mM. [24][25][26] In our study, the cytotoxicity of 1e was determined by CCK-8 assay in human lung cancer H1975 cells ( Fig. 4).…”

“…By comparing the apoptosis induction activity of 1e with other natural derived agents in H1975 cells, 1e exhibited superior anti-cancer activity than cordycepin, but slightly less effective than shikonin. 24,25 Meanwhile, depolarized mitochondria membrane potential was detected aer 24 h treatment with 20 mM of 1e (Fig. 5B).…”

Effects of cordycepin, gold nanostar and their combination on endometrial cancer cells

“…Many studies have shown the anti-cancer properties of cordycepin against various cancers, i.e. liver cancer [17], tongue cancer [18] and breast cancer [19]. The pharmacological mechanism responsible for the anticancer properties of cordycepin is thought to be activation of adenosine A3R, which can inhibit cell growth.…”

The potential application of Cordyceps in metabolic‐related disorders

“…3′‐dATP induced DNA double‐strand breaks, blocked the synthesis of heterogeneous nuclear RNA (hnRNA) and ribosomal RNA (rRNA) precursors via the inhibition on RNA polymerase I and II, impeded the maturation of pre‐messenger RNA (mRNA) and subsequent protein synthesis by competitively inhibiting the poly(A) polymerase‐mediated polyadenylation of pre‐mRNA, and induced cell apoptosis and cell cycle arrest, which together were involved in the antibacterial, antifungal, antiviral, and antitumor activities (Baik et al, ; Lee et al, ; Lee et al, ; Rose, Bell, & Jacob, ). In addition, 3′‐dATP interfered with the binding of ATP, prevented EGFR phosphorylation and its downstream signaling, and inhibited tumor cell proliferation and malignant transformation (Hsu et al, ; Wang et al, ). Cordycepin and/or 3′‐dATP could also promote tumoricidal activities via the enhanced secretion of interferon‐γ and TNF‐α from splenocytes and the downregulation of PD‐L1 expression in tumor cells (Hsu et al, ).…”