title: Capsaicin mediates cell cycle arrest and apoptosis in human colon cancer cells via stabilizing and activating p53.
abstract: Capsaicin is the major pungent ingredient in red peppers which is world widely consumed. Except its potent pain relieving efficacy as reported, capsaicin also exerted its antitumor activity in several tumor models. Here, we reported that capsaicin had a profound anti-proliferative effect on human colon cancer cells via inducing cell cycle G0/G1 phase arrest and apoptosis, which was associated with an increase of p21, Bax and cleaved PARP. The underlying mechanism of capsaicin's antitumor potency was mainly attributed to the stabilization and activation of p53. Capsaicin substantially prolonged the half-life of p53 and significantly elevated the transcriptional activity of p53. Through suppressing the interaction between p53 and MDM2, MDM2-mediated p53 ubiquitination was remarkably decreased after capsaicin treatment, which resulted in the stabilization and accumulation of p53. The results of p53-shRNA experiment further demonstrated that p53 knockdown severely impaired the sensitivity of tested cells to capsaicin, G0/G1 phase arrest and the apoptosis induced by capsaicin in p53-knockdown cells was also dramatically decreased, implicating the important role of p53 played in capsaicin's antitumor activity. In summary, our data suggested that capsaicin, or a related analogue, may have a role in the management of human colon cancer.
authors.affiliation: The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Junzhe
authors.initials: J
authors.lastname: Jin
authors.affiliation: The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Guofu
authors.initials: G
authors.lastname: Lin
authors.affiliation: The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Huang
authors.affiliation: The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Xu
authors.affiliation: The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.affiliation: The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
authors.affiliation: The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Lisi
authors.initials: L
authors.lastname: Zhu
authors.affiliation: The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Dongyan
authors.initials: D
authors.lastname: Ma
authors.affiliation: The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Jiang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology / Q000627:therapeutic use*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D008517:Phytotherapy; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D018689:Sensory System Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018689:Sensory System Agents; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D002211:Capsaicin
keywords: MDM2; capsaicin; colon cancer; p53; ubiquitination.