Asiaticoside suppresses cell proliferation by inhibiting the NF‑κB signaling pathway in colorectal cancer

Zhou,Xin; Ke,Chunlin; Lv,You; Ren,Caihong; Lin,Tiansheng; Dong,Feng; Mi,Yanjun

doi:10.3892/ijmm.2020.4688

Asiaticoside suppresses cell proliferation by inhibiting the NF‑κB signaling pathway in colorectal cancer

Authors:
- Xin Zhou
- Chunlin Ke
- You Lv
- Caihong Ren
- Tiansheng Lin
- Feng Dong
- Yanjun Mi
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Affiliations: Department of Colorectal Cancer, Cancer Center, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, Fujian 361003, P.R. China, Department of Radiotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China, Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China, Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research, The First Affiliated Hospital of Xiamen University, Teaching Hospital of Fujian Medical University, Xiamen, Fujian 361003, P.R. China
Published online on: July 28, 2020 https://doi.org/10.3892/ijmm.2020.4688
Pages: 1525-1537
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer‑associated mortality. Asiaticoside (AC) exhibits antitumor effects; however, to the best of our knowledge, the biological function of AC in CRC cells remains unclear. Therefore, the aim of the present study was to investigate the effect of AC on CRC cells. In the present study, CCK‑8 and colony formation assays were performed to assess the effects of AV on human CRC cell lines (HCT116, SW480 and LoVo). Mitochondrial membrane potential was examined by JC‑1 staining. Cell apoptosis and cell cycle were monitored by flow cytometry, and the expression of genes was evaluated using RT‑qPCR and western blot analysis. Furthermore, the biological effect of AC in vivo was detected using a xenograft mouse model. The findings revealed that 2 µM AC suppressed the proliferation of CRC cells in a time‑ and dose‑dependent manner, but had no adverse effects on normal human intestinal FHC cells at a range of concentrations. AC decreased the mitochondrial membrane potential and increased the apoptosis of CRC cells in a dose‑dependent manner. Furthermore, AC induced cell cycle arrest at the G0/G1 phase. AC attenuated IκBα phosphorylation in a dose‑dependent manner, thereby preventing P65 from entering the nucleus, and resulting in inhibition of the NF‑κB signaling pathway. In addition, AC significantly reduced the expression of CDK4 and Cyclin D1 in a dose‑dependent manner, significantly upregulated the activation of caspase‑9 and caspase‑3, and decreased the Bcl‑2/Bax mRNA ratio. Furthermore, treatment with the NF‑κB signaling pathway inhibitor JSH‑23 significantly increased the cytotoxicity of AC in CRC cells. Findings of the xenograft mice model experiments revealed that AC significantly inhibited colorectal tumor growth in a dose‑dependent manner. Overall, AC suppressed activation of the NF‑κB signaling pathway by downregulating IκBα phosphorylation. This resulted in inhibition of CRC cell viability and an increase of cell apoptosis, which may form the basis of AC use in the treatment of patients with CRC.

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