beta-elemene and Carcinoma--Hepatocellular

Hepatocellular carcinoma (HCC) is a liver malignancy which lacks effective treatment and has a poor prognosis. β-Elemene refers to a natural Curcuma wenyujin-derived single molecular entity, which exhibits various biological activities, and is especially well-known for it's antitumor properties.. LncRNA HOTAIR, SP1, and PDK1 have displayed oncogenic roles in many tumors, participating in the initiation and progression of cancers by mediating multiple signaling pathways. However, there are only a few reports about their roles and mutual relationship in the growth of HCC cells. Therefore, this study aimed to investigate the expression of LncRNA HOTAIR, SP1, and PDK1 and their interaction with β-Elemene in HCC cells.. MTT, a Colony formation assay, and flow cytometry were employed to evaluate the growth of HCC and LO2 cells under β-Elemene. LncRNA HOTAIR, SP1 and PDK1 plasmids were transfected into HCC cells by a transient transfection assay, and the expression and interaction of LncRNA HOTAIR, SP1 and PDK1 were assessed via qRT-PCR and western blotting.. β-Elemene suppressed HCC cell growth through the downregulation of LncRNA HOTAIR, SP1 and PDK1. The results demonstrated a reciprocal interaction among LncRNA HOTAIR, SP1 and PDK1. Exogenous overexpression LncRNA HOTAIR or SP1 eliminated the suppressive effects of β-Elemene on them, and both of which regulated PDK1 expression in HCC cells. Additionally, exogenously overexpressed SP1 or LncRNA HOTAIR prevented β-Elemene inhibition of the protein-level expression of PDK1, whereas overexpressing PDK1 had no effect on SP1, though it still weakened the inhibition of cell growth and LncRNA HOTAIR expression by β-Elemene.. β-Elemene suppresses HCC cell proliferation via through the regulation of LncRNA HOTAIR, SP1, PDK1 and their interaction.

Topics: Antineoplastic Agents, Phytogenic; Carcinoma, Hepatocellular; Cell Line; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Humans; Liver Neoplasms; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; RNA, Long Noncoding; Sesquiterpenes; Sp1 Transcription Factor

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.

Topics: Animals; Carcinoma, Hepatocellular; Cation Transport Proteins; Cell Line, Tumor; Copper Transporter 1; Humans; Liver Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Proteins; Organoplatinum Compounds; Oxaliplatin; Proteolysis; Sesquiterpenes; Xenograft Model Antitumor Assays

To investigate the effects of β-Elemene (β-ELE) on the proliferation, apoptosis, and topoisomerase I (TOPO I) and topoisomerase IIα (TOPO IIα) expression and activity of human hepatocarcinoma HepG-2 cells.. After treatment with β-ELE, morphological alterations of HepG-2 cells were observed under an inverted microscope. Cell proliferation was assessed using an MTT assay, cell cycles were analyzed using flow cytometry, and apoptosis was detected by Annexin V/PI staining. The expression of TOPO I and TOPO IIα was analyzed by Western blot techniques, and their activity was measured using the TOPO I-mediated, supercoiled pBR322 DNA relaxation and TOPO IIα-mediated Kinetoplast DNA (kDNA) decatenation assays, respectively. Supercoiled pBR322 and kDNA were also used to determine the direct effect of β-ELE on DNA breaks.. β-ELE significantly inhibited HepG-2 cell proliferation in a dose- and time-dependent manner. β-ELE also induced tumor cell arrest at S phase, induced cell apoptosis, and downregulated the protein expression of TOPO I and TOPO IIα in a dose-dependent manner. β-ELE also inhibited TOPO I- and TOPO IIα-mediated DNA relaxation but did not directly induce DNA breakage at any concentration.. β-ELE could inhibit the proliferation of HepG-2 cells and interfere with the expression and activity of TOPO I and TOPO IIα.

Topics: Antigens, Neoplasm; Carcinoma, Hepatocellular; Cell Proliferation; DNA Topoisomerases, Type I; DNA Topoisomerases, Type II; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Humans; Liver Neoplasms; Sesquiterpenes