Gigantol inhibits cell proliferation and induces apoptosis by regulating DEK in non‑small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) is a common type of cancer, with a mortality of >80% worldwide. Gigantol is a bibenzyl compound that displays anticancer activity. The aim of the present study was to determine the biological activity of gigantol in NSCLC and to elucidate the underlying molecular mechanism of its action. The expression of DEK proto-oncogene (DEK) was measured in NSCLC tissues and cell lines by reverse transcription-quantitative PCR (RT-qPCR). The results suggested that DEK levels were significantly increased in NSCLC tissues and cell lines compared with adjacent non-tumor tissues and BEAS-2B normal bronchial epithelial cells, respectively. A549 cells were exposed to a series of gigantol concentrations (0, 25, 50 and 100 µM) and transfected with DEK small interfering RNA. The results of cell viability measured by MTT assay indicated that gigantol significantly decreased cell viability. Additionally, cell proliferation was assessed by CCK-8 and apoptosis was measured by flow cytometry. In comparison with the control group, gigantol treatment inhibited cell proliferation and promoted apoptosis, whereas DEK knockdown increased gigantol-induced suppression of proliferation and acceleration of apoptosis. Additionally, DEK overexpression reversed gigantol-induced effects on proliferation and apoptosis. Moreover, compared with the control group, gigantol treatment decreased Ki-67 and Bcl-2 expression levels, increased Bax expression levels and inactivated the Wnt/β-catenin signaling pathway, as assessed by RT-qPCR and/or western blot. DEK knockdown further increased gigantol-induced effects, but DEK overexpression reversed gigantol-induced effects. To conclude, the results of the present study suggested that gigantol inhibited cell proliferation and induced apoptosis by decreasing Ki-67 and Bcl-2 expression, increasing Bax expression and activating the Wnt/β-catenin signaling pathway by regulating DEK. The present study indicated the therapeutic potential of gigantol in patients with NSCLC. In addition, DEK may serve as a novel therapeutic target to enhance the effects of gigantol treatment.

The m6A Methyltransferase METTL3-Mediated N6-Methyladenosine Modification of DEK mRNA to Promote Gastric Cancer Cell Growth and Metastasis

“…Additionally, DEK is overexpressed in high-grade serous ovarian cancers (HGSOCs), and reducing DEK levels significantly reduces cell viability and tumor growth, resulting in apoptotic cell death [ 38 ]. Cai et al showed that Gigantol inhibits cell proliferation and induces apoptosis by regulating DEK in non-small cell lung cancer [ 39 ]. In the report on GC, Lee et al reported that DEK is a potential biomarker associated with malignant phenotype in GC Tissues and Plasma [ 40 ], and Fan et al demonstrated that circ_0000039 upregulates DEK expression by adsorbing miR-1292-5p, promoting the proliferation and progression of GC cells [ 41 ].…”

Targeting Cell Signaling Pathways in Lung Cancer by Bioactive Phytocompounds

“…In lung cancer cell line A549, gigantol has been shown to suppress cell proliferation and enhance apoptosis in tumor cells at a concentration of 25, 50, and 100 µM. Investigators report these effects to be mediated by inhibition of Bcl-2 expression and upregulation of Bax expression and Wnt/β-catenin signaling [224]. In another study, gigantol has been shown to inhibit cell proliferation in H460 lung cancer cells at a concentration of 50 µM.…”

Targeted therapy for non‐small‐cell lung cancer: New insights into regulated cell death combined with immunotherapy

“…Additionally, treatment with 20 μM Andro caused an essential decrease in the mitochondrial membrane potential (MMP), an increase in Bak mitochondrial translocation, and an increase in the activation of proteins in the mitochondrion-mediated intrinsic apoptosis pathway. 38 TA B L E 3 (Continued)…”

“…Among these derivates, Compound 17 (38) exerted excellent anticancer activity against H460 and H322 cells (IC 50 = 2.6 ± 0.9 μM and 3.3 ± 0.9 μM, respectively). It induced autophagy by TA B L E 4 (Continued)…”

“…Treatment with 5 μM Andro reduced the proliferative rate of H1975 cells by 60%. Additionally, treatment with 20 μM Andro caused an essential decrease in the mitochondrial membrane potential (MMP), an increase in Bak mitochondrial translocation, and an increase in the activation of proteins in the mitochondrion‐mediated intrinsic apoptosis pathway 38 . A group of compounds known as carbon monoxide‐releasing molecules (CO‐RMs) transport and release controlled quantities of carbon monoxide within cells.…”