title: Arecoline decreases interleukin-6 production and induces apoptosis and cell cycle arrest in human basal cell carcinoma cells.
abstract: Arecoline, the most abundant areca alkaloid, has been reported to decrease interleukin-6 (IL-6) levels in epithelial cancer cells. Since IL-6 overexpression contributes to the tumorigenic potency of basal cell carcinoma (BCC), this study was designed to investigate whether arecoline altered IL-6 expression and its downstream regulation of apoptosis and the cell cycle in cultured BCC-1/KMC cells. BCC-1/KMC cells and a human keratinocyte cell line, HaCaT, were treated with arecoline at concentrations ranging from 10 to 100μg/ml, then IL-6 production and expression of apoptosis- and cell cycle progress-related factors were examined. After 24h exposure, arecoline inhibited BCC-1/KMC cell growth and decreased IL-6 production in terms of mRNA expression and protein secretion, but had no effect on HaCaT cells. Analysis of DNA fragmentation and chromatin condensation showed that arecoline induced apoptosis of BCC-1/KMC cells in a dose-dependent manner, activated caspase-3, and decreased expression of the anti-apoptotic protein Bcl-2. In addition, arecoline induced progressive and sustained accumulation of BCC-1/KMC cells in G2/M phase as a result of reducing checkpoint Cdc2 activity by decreasing Cdc25C phosphatase levels and increasing p53 levels. Furthermore, subcutaneous injection of arecoline led to decreased BCC-1/KMC tumor growth in BALB/c mice by inducing apoptosis. This study demonstrates that arecoline has potential for preventing BCC tumorigenesis by reducing levels of the tumor cell survival factor IL-6, increasing levels of the tumor suppressor factor p53, and eliciting cell cycle arrest, followed by apoptosis.
authors: Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
authors: Li-Wen
authors: LW
authors: Huang
authors: Bau-Shan
authors: BS
authors: Hsieh
authors: Hsiao-Ling
authors: HL
authors: Cheng
authors: Yu-Chen
authors: YC
authors: Hu
authors: Wen-Tsan
authors: WT
authors: Chang
authors: Kee-Lung
authors: KL
authors: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001115:Arecoline / Q000008:administration & dosage / Q000494:pharmacology*; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000096:biosynthesis*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism
chemical_list: D002843:Chromatin; D015850:Interleukin-6; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D001115:Arecoline; D053148:Caspase 3