Cordycepin Induces S Phase Arrest and Apoptosis in Human Gallbladder Cancer Cells

Abstract

Gallbladder cancer is the most common malignant tumor of the biliary tract, and this condition has a rather dismal prognosis, with an extremely low five-year survival rate. To improve the outcome of unresectable and recurrent gallbladder cancer, it is necessary to develop new effective treatments and drugs. The purpose of the present study was to evaluate the effects of cordycepin on human gallbladder cells and uncover the molecular mechanisms responsible for these effects. The Cell Counting Kit-8 (CCK-8) and colony formation assays revealed that cordycepin affected the viability and proliferation of human gallbladder cancer cells in a dose-and time-dependent manner. Flow cytometric analysis showed that cordycepin induced S phase arrest in human gallbladder cancer cell lines(NOZ and GBC-SD cells). Cordycepin-induced apoptosis was observed using an Annexin V/propidium iodide (PI) double-staining assay, and the mitochondrial membrane potential OPEN ACCESSMolecules 2014, 19 11351 (ΔΨm) decreased in a dose-dependent manner. Additionally, western blot analysis revealed the upregulation of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP and Bax and the downregulation of Bcl-2, cyclin A and Cdk-2 in cordycepin-treated cells. Moreover, cordycepin inhibited tumor growth in nude mice bearing NOZ tumors. Our results indicate that this drug may represent an effective treatment for gallbladder carcinoma.

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

“…caspase-3 and Bax were associated with the apoptotic effect of cordycepin on H1975 cells. These results were consistent with the previous study where cordycepin induced apoptosis via downregulating the protein level of caspase-3 and Bcl-2 [25]. …”

“…These indicated that down-regulation of caspase-3 and Bcl-2 and up-regulation of cleaved caspase-3 and Bax were associated with the apoptotic effect of cordycepin on H1975 cells. These results were consistent with the previous study where cordycepin induced apoptosis via down-regulating the protein level of caspase-3 and Bcl-2 [25]. caspase-3 and Bax were associated with the apoptotic effect of cordycepin on H1975 cells.…”

Japonicone A inhibits the growth of non-small cell lung cancer cells via mitochondria-mediated pathways

“…Our results showed that japonicone A treatment decreased the ΔΨm in all NSCLC cell lines, which indicates that japonicone A-induced apoptosis in NSCLC cells occurs via the mitochondria-related pathway. The disruption of the ΔΨm is recognized as an early stage of apoptosis, where the release of cytochrome c from mitochondria signals the initiation of apoptosis [15,16]. The mitochondria-dependent pathway is regulated by Bcl-2 family proteins, which are involved in apoptosis involving the pro-apoptotic proteins Bax [17,18].…”

Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases

“…Data suggest that mitochondrial Ca 2++ handling accounts for spontaneous electrical activity, a step involved in gallbladder tone and motility (Balemba et al, 2008). Gallbladder mitochondria are also involved in other pathways such as drug-mediated effects on apoptosis during tumorigenesis in cells and mice (Bao et al, 2014;Li et al, 2015a;Liu et al, 2013;Shu et al, 2014;Wang et al, 2014;Weng et al, 2014) and treatment with oxysterols causing cytochrome c release in the dog (Seo et al, 2004). Both aspects are potentially linked to the aging process of the gallbladder with or without stone-formation ability.…”