β-elemene sensitizes hepatocellular carcinoma cells to oxaliplatin by preventing oxaliplatin-induced degradation of copper transporter 1.

Abstract

β-elemene, a Curcuma wenyujin plant extract, has been used widely as a tumor adjuvant therapeutic agent. However, how to obtain optimum therapeutic effects by combining this compound with other agents remain unclear. In this study, we found that β-elemene, which alone had little effect on hepatocellular carcinoma (HCC) cell proliferation, exerted a synergistic anti-proliferative effect in HCC cells when dosed in combination with oxaliplatin, which increased the amounts of platinum accumulation and platinum-DNA adduct significantly and augmented the oxaliplatin-induced apoptosis. Western blot and laser scanning confocal microscopy studies indicated that β-elemene enhanced the sensitivity of HCC cells to oxaliplatin by upregulating copper transporter 1 (CTR1), a major controller of intracellular platinum accumulation. In an orthotopic transplantation HCC model in nude mice, HCC tumor growth was inhibited significantly by oxaliplatin combined with β-elemene, as compared with oxaliplatin alone. Notably, CTR1 protein expression in xenograft HCC was upregulated in mice who received β-elemene treatment. Taken together, our findings show that β-elemene can block the reduction of CTR1 resulting from oxaliplatin treatment, and therefore has a synergistic anti-HCC effect with oxaliplatin by enhancing cellular uptake of oxaliplatin. The synergistic effects of β-elemene and oxaliplatin deserve further evaluation in clinical settings.

• Authors: Xiaoqiang Li, Zhenhai Lin, Bo Zhang, Lei Guo, Shuang Liu, Hui Li, Jubo Zhang, Qinghai Ye
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 21010 (Feb 12 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 26867799 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cation Transport Proteins
• Copper Transporter 1
• Neoplasm Proteins
• Organoplatinum Compounds
• SLC31A1 protein, human
• Sesquiterpenes
• beta-elemene
• Oxaliplatin

Topics

• Animals
• Carcinoma, Hepatocellular (drug therapy, genetics, metabolism, pathology)
• Cation Transport Proteins (genetics, metabolism)
• Cell Line, Tumor
• Copper Transporter 1
• Humans
• Liver Neoplasms (drug therapy, genetics, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Proteins (genetics, metabolism)
• Organoplatinum Compounds (pharmacology)
• Oxaliplatin
• Proteolysis (drug effects)
• Sesquiterpenes (pharmacology)
• Xenograft Model Antitumor Assays