title: Anti-cancer activity of highly purified sulfur in immortalized and malignant human oral keratinocytes.
abstract: Sulfur is commonly used in Asia as an herbal medicine to treat inflammation and cancer, and potent chemopreventive effects have been demonstrated in various in vivo and in vitro models for sulfur-containing compounds found in naturally occurring products. Here, we report the growth inhibitory and apoptosis-related effects of a newly developed highly purified sulfur (HPS) on immortalized human oral keratinocytes (IHOKs) and on oral cancer cells representing two stages of oral cancer (HN4, HN12) based on a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Western blotting, cell cycle analysis, and nuclear staining. The purity of the sulfur preparation was verified by high-performance liquid chromatography. HPS inhibited the proliferation of immortalized and malignant oral keratinocytes in a dose- and time-dependent manner. FITC-annexin V staining, DNA fragmentation testing, and Hoechst 33258 staining revealed that HPS inhibited cell growth via apoptosis. HPS increased the sub-G1 cell cycle fraction, with decreased expression of cyclins D1, D2, and E and their activating partners cdk2, cdk4, and cdk6, and a concomitant induction of p53 and p21/WAF1. Furthermore, HPS treatment increased the cytosolic level of cytochrome c and resulted in caspase-3 activation; this effect was correlated with Bax up-regulation and Bcl-2 down-regulation. Thus, these data suggest that HPS is a potential candidate for anti-cancer therapy in oral cancer.
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Dentistry, Wonkwang University, Iksan, South Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Lee
authors.forename: Hwa-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jong-Dae
authors.initials: JD
authors.lastname: Park
authors.forename: Sun-Kyung
authors.initials: SK
authors.lastname: Lee
authors.forename: Sang-Im
authors.initials: SI
authors.lastname: Lee
authors.forename: Hyun-Dae
authors.initials: HD
authors.lastname: Lim
authors.forename: You-Mee
authors.initials: YM
authors.lastname: Lee
authors.forename: Young-Gab
authors.initials: YG
authors.lastname: Yun
authors.forename: Byung-Hun
authors.initials: BH
authors.lastname: Jeon
authors.forename: In-Soo
authors.initials: IS
authors.lastname: Ree
authors.forename: Chang-Duk
authors.initials: CD
authors.lastname: Jun
authors.forename: Suk-Keun
authors.initials: SK
authors.lastname: Lee
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016213:Cyclins / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology; D009062:Mouth Neoplasms / Q000188:drug therapy*; D009367:Neoplasm Staging; D013457:Sulfur Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D016213:Cyclins; D013457:Sulfur Compounds