Anticancer effects of β-elemene with hyperthermia in lung cancer cells

Abstract

Abstract. β-elemene is a novel, plant-derived anticancer drug, which has been used to target multiple solid tumor types. Hyperthermia is an adjuvant therapeutic modality to treat cancer. However, the underlying mechanisms associated with the efficacy of these two treatments are largely unknown. The aim of the present study was to evaluate the effects of β-elemene combined with hyperthermia in lung cancer cell lines. An MTT assay was used to determine cell viability. The cell cycle and apoptosis were analyzed using flow cytometry. The morphology of cells during apoptosis was determined using a transmission electron microscope. The expression levels of P21, survivin, caspase-9, B-cell lymphoma 2 (Bcl-2) and Bcl-2-like protein 4 (Bax) mRNA were detected using quantitative polymerase chain reaction. β-elemene with hyperthermia treatment significantly inhibited the viability and increased the apoptosis rate of A549 cells compared with β-elemene treatment alone (P<0.01), and significantly decreased the proportion of cells in S phase compared with the control (P<0.01). Morphological observation using transmission electron microscopy indicated cross-sectional features of apoptosis: Chromatin condensation, reduced integrity of the plasma membrane, increased cellular granularity, nuclear collapse and the formation of apoptotic bodies. β-elemene with hyperthermia treatment significantly promoted P21 and Bax mRNA expression (P<0.01) and significantly decreased caspase-9, Bcl-2 and survivin mRNA expression (P<0.01) in A549 cells. In conclusion, β-elemene with hyperthermia has a significant inhibitory effect on A549 cells. This occurs through reducing S phase and inducing apoptosis, via an increase in P21 and Bax expression and a decrease in caspase-9, Bcl-2 and survivin expression.

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

“…It also inhibits cell proliferation and invasion, and induces apoptosis via inhibition of Wnt/β-catenin signaling pathway in human cervical cancer SiHa cells [749]. β-elemene-induced apoptosis is also shown to be through mitochondrial-related pathways, including p21 and Bax up-regulation, caspase-9 activation, Bcl-2 and survivin down-regulation [754]. On the other hand, it reverses drug resistance through mitochondrial-mediated apoptosis in human NSCLC cisplatin-resistant A549/DDP cells, via cytochrome c release, caspase-3 activation, Bcl-2 associated agonist of cell death (Bad) up-regulation and Bcl-2 down-regulation [761].…”

“…β-Elemene is shown to induce apoptosis in human cervical cancer SiHa, NSCLC A549 cells, primary bladder cancer cells, and Burkitt's lumphoma, and inhibit tumor growth in Lewis tumor-bearing mice [746,747,749,753,754]. It up-regulates insulin-like growth factorbinding protein 1 (IGFBP1) to induce a reciprocal interaction between microRNA 155-5p and FoxO3a, which leads to the inhibition of cell growth in human NSCLC A549 and H1975 cells [755].…”

“…It up-regulates insulin-like growth factorbinding protein 1 (IGFBP1) to induce a reciprocal interaction between microRNA 155-5p and FoxO3a, which leads to the inhibition of cell growth in human NSCLC A549 and H1975 cells [755]. β-Elemene also induces S phase arrest in human NSCLC A549 cells [754], while it induces G0/G1 phase arrest in human glioblastoma U87 cells [756]. Moreover, it induces protective autophagy in human gastric cells MGC-803 and SGC-7901, and NSCLC A549 cells, as autophagy inhibition promotes β-elemene-induced anti-tumor effects [748,757].…”

Simple Trans-Platinum Complex Bearing 3-Aminoflavone Ligand Could Be a Useful Drug: Structure-Activity Relationship of Platinum Complex in Comparison with Cisplatin

“…In the present study, cytostatics with hyperthermia induced apoptosis in ovarian cancer cells OVCAR-3 and Caov-3 by increasing the expression of BAX and CASP3 and reducing the expression of BIRC5. Many studies currently analyse the effects of elevated temperatures on cell survival in a cytostatic environment [71][72][73]. As a result, the expression of survivin and induction of apoptosis is reduced.…”

Drug delivery systems for elemene, its main active ingredient &beta;-elemene, and its derivatives in cancer therapy

“…3 Chemotherapeutic drugs, such as 5-fluorouracil, temozolomide (TMZ), cisplatin, gefitinib, endostar, etoposide, rapamycin, oxaliplatin, taxanes, and ligustrazine, as well as radiotherapy and hyperthermia, could improve the antitumor effects and reverse multiple-drug resistance (MDR) in combination with β-elemene. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] In recent years, the study of mechanism of action of β-elemene has made great progress. β-elemene exerts its effects by modulating multiple molecular targets.…”