The effect of elemene on lung adenocarcinoma A549 cell radiosensitivity and elucidation of its mechanism

Abstract

OBJECTIVE:To investigate the effect of elemene on the radiosensitivity of A549 cells and its possible molecular mechanism.METHODS:Apoptosis of A549 cells was detected by flow cytometry and fluorescence microscopy. The effect of double-strand break (DSB) damage repair in A549 cells was evaluated using the neutral comet assay. Protein expression levels were detected using western blotting, and the correlation between protein levels was analyzed.RESULTS:Elemene exhibited a radiosensitizing effect on A549 cells. The level of apoptosis induced by elemene combined with radiation was significantly greater (p<0.01) than that elicited by either radiation or elemene alone. Following radiation and subsequent repair for 24 h, the tail intensity of A549 cells treated with a combination of elemene and radiation was greater than that of cells treated with either elemene or radiation alone (p<0.01). This result indicates that elemene inhibits cellular DSB repair. Both elemene combined with radiation and radiation alone decreased the protein expression of DNA-PKcs and Bcl-2 compared to elemene alone (p<0.01), while p53 protein expression was increased (p<0.01). A negative correlation was observed between DNA-PKcs and p53 expression (r=-0.569, p=0.040), while a positive correlation was found between DNA-PKcs and Bcl-2 expression (r=0.755, p=0.012).CONCLUSIONS:Elemene exhibits a radiosensitizing effect on A549 cells, and its underlying molecular mechanism of action may be related to the downregulation of DNA-PKcs gene expression.

Comparative Efficacy of Whole-Brain Radiotherapy with and without Elemene Liposomes in Patients with Multiple Brain Metastases from Non-Small-Cell Lung Carcinoma

“…Jiang et al 15 showed that, in addition to promoting tumour cell apoptosis directly, β-elemene also exerts a radiosensitizing effect on lung adenocarcinoma A549 cells through upregulation of p53 expression and inhibition of Bcl-2 expression. Another study by Zou et al 16 demonstrated that the molecular mechanisms responsible for the radiosensitizing effect might involve the downregulation of dna-dependent protein kinase catalytic subunit gene expression. Li et al 17 established a lung tumour model in female athymic BALB/cnu/nu mice, and showed that β-elemene (45 mg/kg) had the potential to reduce radiation-induced expression of survivin and hypoxia inducible factor 1a proteins, which were probably the targets of β-elemene.…”

Regulation of signaling pathways by β‐elemene in cancer progression and metastasis

“…Detailed mechanistic insights unraveled that β-elemene in combination with radiation drastically reduced protein levels of DNA damage repair associated kinase (DNA-PKcs). 37 ATM played a major role in the DNA damage response and repair. Treatment of glioblastoma cells with β-elemene decreased the phosphorylation of ATM, PKB/AKT, and ERK following chemotherapy or radiotherapy.…”

<p>Down-Regulation of Hypoxia-Inducible Factor-1α and Downstream Glucose Transporter Protein-1 Gene by β-elemene Enhancing the Radiosensitivity of Lung Adenocarcinoma Transplanted Tumor</p>

“…Elemene, extracted from Rhizoma Zedoariae, is a terpene compound with an immunomodulatory effect, and the radiosensitization of β-elemene has been confirmed as the main anti-tumor component of elemene. 3 Although it has multiple effects such as the inhibition of tumor angiogenesis, promotion of tumor cell G-M phase arrest, induction of tumor cell apoptosis, and repairment of Deoxyribonucleic acid (DNA) double-strand damage, [4][5][6] its sensitizing mechanism still remains poorly understood.…”