Downregulation ofMDR1Gene by Cepharanthine Hydrochloride Is Related to the Activation of c-Jun/JNK in K562/ADR Cells

Abstract

The purpose of the study was to determine the signal transduction mechanism of cepharanthine hydrochloride (CH) on reversing tumor multidrug resistance. RT-PCR and Western blot analysis were used to determine the effects of CH on the expression of MDR1 mRNA and P-glycoprotein in K562/ADR cells when CH was used alone and combined with SP600125, a JNK inhibitor, to explore the effects of CH on JNK pathway. Western blot analysis was used to determine the effects of CH on c-Jun protein expression and phosphorylation, to explore the regulating effects of CH on c-Jun and phosphorylated c-Jun (p-c-Jun) proteins. Our results showed that the inhibitory effect of CH on MDR1 mRNA increased with the concentrations of CH (5.0, 10.0, and 20.0 μM) and the inhibitory effects of CH on MDR1 mRNA and P-glycoprotein increased with the incubation time of CH (0, 12, 24, 36, and 48 hours). The inhibitory effect was weakened after CH combined with SP600125. The expressions of c-Jun and p-c-Jun proteins increased with the incubation time of CH (0, 6, 12, and 24 hours). These findings suggest that CH downregulated the expressions of MDR1 mRNA and P-glycoprotein in a time and concentration manner; the mechanism may be mediated via activating c-Jun/JNK pathway.

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…It exhibits antimalarial, anti-viral, anti-inflammatory, anti-metastatic, and anti-cancer activities in various cell lines and animal models [772,[774][775][776]. Among its anti-cancer activities, CEP exhibits multiple pharmacological actions, including apoptosis and radiation sensitization, inhibition of angiogenesis and metastasis, and reversing MDR [776][777][778][779][780][781][782][783][784][785][786][787][788][789].…”

“…Targeting P-gp using P-gp inhibitors is one of the main strategies to reverse MDR, and cepharanthine hydrochloride (CEH), a salt form of CEP, is suggested to be a potent P-gp inhibitor [779]. CEH exhibits MDR reversal potency in various cancer cells [779][780][781]788]. CEH can reverse MDR-mediated cisplatin resistance in esophageal squamous cell carcinoma [780].…”

Solanine reverses multidrug resistance in human myelogenous leukemia K562/ADM cells by downregulating MRP1 expression

“…The c-Jun N-terminal kinases (JNK) belong to the mitogen-activated protein kinase (MAPK) family (12). There are three JNK isoforms in mammals, JNK1, JNK2 and JNK3, which are encoded by the MAPK8, MAPK9 and MAPK10 genes, respectively (13).…”

“…The JNK signaling pathway has been reported to be involved in cellular proliferation, apoptosis and differentiation, and tumor cell migration (16,17). Increasing evidence has indicated that JNK activity serves an important role in the development of chemoresistance and is associated with MRP1 expression (12)(13)(14)(15)(16).…”

Retracted: Downregulation of MDR1 Gene by Cepharanthine Hydrochloride Is Related to the Activation of c-Jun/JNK in K562/ADR Cells

“…BioMed Research International has retracted the article titled “Downregulation of MDR1 Gene by Cepharanthine Hydrochloride Is Related to the Activation of c-Jun/JNK in K562/ADR Cells.” [1]. β -Actin loading controls in the Western Blots were duplicated.…”