Nitidine chloride inhibits proliferation and induces apoptosis in colorectal cancer cells by suppressing the ERK signaling pathway

Zhai,Huiyuan; Hu,Sanyuan; Liu,Tongxiang; Wang,Feng; Wang,Xixun; Wu,Guochang; Zhang,Yifei; Sui,Minghua; Liu,Huantao; Jiang,Lixin

doi:10.3892/mmr.2016.4827

Nitidine chloride inhibits proliferation and induces apoptosis in colorectal cancer cells by suppressing the ERK signaling pathway

Authors:
- Huiyuan Zhai
- Sanyuan Hu
- Tongxiang Liu
- Feng Wang
- Xixun Wang
- Guochang Wu
- Yifei Zhang
- Minghua Sui
- Huantao Liu
- Lixin Jiang
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Affiliations: Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Emergency, People's Hospital of Weifang, Weifang, Shandong 261041, P.R. China, Department of Breast Disease, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Department of Abdominal Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China
Published online on: January 29, 2016 https://doi.org/10.3892/mmr.2016.4827
Pages: 2536-2542
Copyright: © Zhai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Nitidine chloride (NC) is a natural bioactive phytochemical alkaloid that has displayed anticancer activity in various types of cancer. However, no evidence has been reported for the direct effect of NC on CRC cell proliferation and apoptosis, and the underling mechanisms to be fully elucidated. The present study aimed to investigate the influence of NC on the apoptosis and proliferation of CRC cells. The viability and proliferation of CRC cells was measured by MTT assay and a [3H] thymidine uptake assay. Apoptosis was measured using a flow cytometric apoptosis assay and TUNEL staining. The expression levels of apoptotic‑regulated proteins in addition to extracellular signal‑regulated kinase (ERK) were measured by western blot analysis following stimulation with NC. The results indicated that NC inhibited the proliferation of HCT116 cells in a dose‑ and time‑dependent manner. Additionally, apoptotic induction by NC treatment was confirmed. Furthermore, NC was demonstrated to significantly upregulate the expression of Bax, p53, cleaved caspase‑3 and ‑9 and downregulate the expression of Bcl‑2. Treatment with NC reduced the phosphorylation of ERK and by using an ERK inhibitor, U0126, the roles of NC in apoptotic induction and the inhibition of proliferation were further demonstrated. These results demonstrated that NC inhibited the proliferation and induced the apoptosis of CRC cells via the ERK signaling pathway.

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