title: Dracorhodin perchlorate induces apoptosis in primary fibroblasts from human skin hypertrophic scars via participation of caspase-3.
abstract: Hypertrophic scar (HS) is an abnormally proliferative disorder characterized by excessive proliferation of fibroblasts and redundant deposition of extracellular matrix. An unbalance between fibroblast proliferation and apoptosis has been assumed to play an important role in HS formation. To explore the regulative effects of dracorhodin perchlorate (Dp), one of the derivants of dracorhodin that is a major constituent in the traditional Chinese medicine, on primary fibroblasts from human skin hypertrophic scars, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis were respectively used to evaluate the inhibitory effect of Dp on the cells and to determine cell cycle distribution. Additionally, cellular apoptosis was separately detected with Hoechst 33258 staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. The expression levels of caspase-3 mRNA and protein were respectively measured with reverse transcription-polymerase chain reaction and western blot analysis, and caspase-3 activity were determined using a colorimetric assay kit. The results showed that Dp significantly inhibited cell growth, and induced apoptosis in fibroblasts in a dose-and time-dependent manner, arresting cell cycle at G1 phase. Additionally, Dp slightly up-regulated caspase-3 mRNA expression in fibroblasts, but significantly down-regulated caspase-3 protein expression in a dose- and time-dependent manner, and concurrently elevated caspase-3 activity. Taken together, these data indicated that Dp could effectively inhibit cell proliferation, and induced cell cycle arrest and apoptosis in fibroblasts, at least partially via modulation of caspase-3 expression and its activity, which suggests that Dp is an effective and potential candidate to develop for HS treatment.
authors: Institute of Plastic Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong Province, China.
authors: Peihua
authors: P
authors: Zhang
authors: Institute of Plastic Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong Province, China.
authors: Jin
authors: J
authors: Li
authors: Institue of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang 524023, Guangdong Province, China.
authors: Xudong
authors: X
authors: Tang
authors: Institute of Plastic Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong Province, China.
authors: Junlei
authors: J
authors: Zhang
authors: Institute of Plastic Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong Province, China.
authors: Jie
authors: J
authors: Liang
authors: Institute of Plastic Surgery, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, Guangdong Province, China. Electronic address: Guofangz@yahoo.com.
authors: Guofang
authors: G
authors: Zeng
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D015394:Molecular Structure; D061251:Primary Cell Culture; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D055815:Young Adult
chemical_list: D001578:Benzopyrans; D004365:Drugs, Chinese Herbal; C060327:dracorhodin; D053148:Caspase 3
keywords: Apoptosis; Caspase-3; Dracorhodin perchlorate; Fibroblasts; Hypertrophic scar