title: Nitidine chloride inhibits proliferation and induces apoptosis in colorectal cancer cells by suppressing the ERK signaling pathway.
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.
authors: Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors: Huiyuan
authors: H
authors: Zhai
authors: Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors: Sanyuan
authors: S
authors: Hu
authors: Department of Emergency, People's Hospital of Weifang, Weifang, Shandong 261041, P.R. China.
authors: Tongxiang
authors: T
authors: Liu
authors: Department of Breast Disease, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
authors: Feng
authors: F
authors: Wang
authors: Department of Abdominal Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
authors: Xixun
authors: X
authors: Wang
authors: Department of Abdominal Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
authors: Guochang
authors: G
authors: Wu
authors: Department of Abdominal Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
authors: Yifei
authors: Y
authors: Zhang
authors: Department of Abdominal Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
authors: Minghua
authors: M
authors: Sui
authors: Department of General Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
authors: Huantao
authors: H
authors: Liu
authors: Department of Abdominal Surgery, Yantai Yuhuangding Hospital, Yantai, Shandong 264000, P.R. China.
authors: Lixin
authors: L
authors: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053119:Benzophenanthridines / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D045325:HCT116 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C000595707:BCL2 protein, human; D053119:Benzophenanthridines; D019253:Proto-Oncogene Proteins c-bcl-2; C013615:nitidine; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9