Therapeutic effects of β-elemene via attenuation of the Wnt/β-catenin signaling pathway in cervical cancer cells

Abstract

Concurrent radio chemotherapy treatment prolongs the survival rate of patients with advanced cervical cancer; however, it has adverse side-effects. β-elemene, an active component of the traditional Chinese medicinal herb Curcuma zedoaria, is a promising alternative therapeutic drug for the treatment of advanced cervical cancer. The aim of the present study was to investigate the antitumor effects of β-elemene in human cervical cancer SiHa cells and to determine its underlying therapeutic molecular mechanisms. Cell viability, cell cycle progression and apoptosis were detected using an MTT assay and flow cytometry analysis. Furthermore, the levels of cell migration and cell invasion were investigated using Transwell and wound healing assays. The expression levels of Cyclin-dependent kinase inhibitor 2B (P15), Cyclin D1, cellular tumor antigen p53, apoptosis regulator Bcl-2 (Bcl-2), apoptosis regulator BAX (Bax), 72 kDa type IV collagenase (MMP-2), matrix metalloproteinase-9 (MMP-9), β-catenin, transcription factor 7 (TCF7), and Myc proto-oncogene protein (c-Myc) were analyzed via western blotting. The results revealed that β-elemene inhibited the proliferation of SiHa cells in a dose and time-dependent manner. Administration of β-elemene induced G1 phase cell-cycle arrest, as demonstrated by the upregulation of P15 expression and the downregulation of Cyclin D1 expression. Furthermore, the present study revealed that β-elemene induced apoptosis in SiHa cells by enhancing the expression of p53 and Bax, and suppressing the expression of Bcl-2. In addition, treatment with β-elemene inhibited cell migration and invasion via downregulation of MMP-2 and MMP-9 expression levels. Western blotting demonstrated that β-elemene reduced the expression levels of β-catenin and its downstream target molecule TCF7, thus resulting in reduced levels of their target proteins, including c-Myc, Cyclin D1, Bax and MMP-2 in cervical cancer cells. The results of the present study suggested that β-elemene may inhibit cell proliferation and invasion, in addition to inducing apoptosis, via attenuation of the Wnt/β-catenin signaling pathway in cervical cancer cells.

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

“…It has various pharmacological effects including anti-oxidative, anti-inflammatory and anti-cancer activities [744][745][746]. It exerts anti-cancer effects in many cancers, such as lung, gastric, cervical, breast and bladder cancers, osteosarcoma, through apoptosis, inhibition of cell proliferation, migration and invasion, angiogenesis [746][747][748][749][750][751][752].…”

“…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].…”

Astragaloside IV inhibits cell proliferation in vulvar squamous cell carcinoma through the TGF‐β/Smad signaling pathway

“…Although immunotherapy and targeted therapy are used in many tumors, these treatments are rarely used in VSCC patients at present. Some traditional Chinese medicines have been confirmed to be effective anti‐tumor agents (Song, Yang, Bai, & Ji, ; Wang, Zhao, Wu, Guan, & Wu, ; Wu et al, ). However, there have been no reports regarding the research on AS‐IV in VSCC.…”

“…*p < 0.05; **p < 0.01 as indicated. NC, the negative control; TGF-β1, transforming growth factor-β1 anti-tumor agents (Song, Yang, Bai, & Ji, 2011;Wang, Zhao, Wu, Guan, & Wu, 2018;Wu et al, 2018). However, there have been no reports regarding the research on AS-IV in VSCC.…”

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

“…Furthermore, β-elemene regulates several key molecules of tumor angiogenesis and metastasis, such as VEGF and matrix metalloproteinase, in addition to modulating the expression of ncRNAs that contribute to anticancer activities. [21][22][23][24][25][26][27][28][29][30][31][32][33][34] However, the clinical application of elemene has been limited by its poor solubility in water, poor stability, and low bioavailability. Therefore, studying a new drug delivery system for elemene has important significance.…”