Effect of arenobufagin on human pancreatic carcinoma cells

Abstract

Abstract. Pancreatic carcinoma (PC) is a deadly form of cancer with poor overall survival. Currently, chemotherapy such as gemcitabine and 5-fluorouracil (5-FU) are the most popular medications that can improve survival, but rapid drug-resistance makes the search for more effective drugs urgent. Upon looking for natural components to treat PC, it was found that arenobufagin, a cardiac glycosides-like compound, showed significant effects on the gemcitabine-resistant pancreatic carcinoma cell line Panc-1 and the gemcitabine-sensitive cell line ASPC-1 at nanomolar concentrations. The present study used MTT and clonogenic survival assays to examine survival and proliferation, and western blotting to assess changes in the associated mitogen activated protein kinase and phosphoinositide 3-kinase pathways and expression of apoptosis-related proteins. The current study also detected the cell cycle by flow cytometry. Arenobufagin inhibited cell survival and proliferation, decreased the phosphorylation of key downstream proteins of K-Ras, including protein kinase B and extracellular signal related kinase, induced cell cycle G2/M phase arrest and apoptosis, and downregulated the level of phosphorylated epidermal growth factor receptor. Notably, the present data also showed that arenobufagin can enhance the sensitivity of PC cells to gemcitabine and 5-FU. In conclusion, arenobufagin could enhance the effect of gemcitabine and 5-FU on PC cells by targeting multiple key proteins. Therefore, arenobufagin has potential as anadjuvant therapy for the treatment of PC.

Evaluation of Helium Ion Radiotherapy in Combination with Gemcitabine in Pancreatic Cancer In Vitro

“…The results of gemcitabine treatment proved Panc-1 to be gemcitabine-resistant compared to the other cell lines, which has been described in the literature [27]. In accordance with this observation, Panc-1 cells have shown slight additive effects after combined therapy with gemcitabine.…”

Arenobufagin Promoted Oxidative Stress‐Associated Mitochondrial Pathway Apoptosis in A549 Non‐Small‐Cell Lung Cancer Cell Line

“…Arenobufagin (ARE, structure shown in Figure 1(a)), one of the effective constituents of toad venom, is a traditional Chinese medicine obtained from the skin and parotid venom glands of Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider [11]. Anyway, a lot of studies have demonstrated its broadspectrum antitumor activities in cancers such as breast cancer, pancreatic carcinoma, and liver cancer [12][13][14]. We previously found that ARE can induce liver cancer cell apoptosis and autophagy through PI3K/Akt/mTOR signal routing [14]; induce cell cycle arrest and apoptosis in human cervical cancer HeLa cells [15]; have anticancer effect on human esophageal squamous cell carcinoma (its mechanism of exerting anticancer efficacy may be activation of cysteinecontaining aspartate proteolytic enzyme (caspase) by endogenous and exogenous pathways); promote apoptosis of esophageal cancer cells by enhancing caspase phosphorylation and activating p53 signaling [16]; promote apoptosis of human glioblastoma U-87 cells by inhibiting p38MAPK signaling pathway [17]; and inhibit epithelial-mesenchymal conversion by going down the β-catenin pathway, consequently repressing motility and invasiveness of prostate cancer PC3 cells [18].…”