Functional and mechanistic investigation of Shikonin in scarring. (25th February 2015)

• Record Type: Journal Article
• Authors: Xie, Yan; Fan, Chen; Dong, Ying; Lynam, Emily; Leavesley, David I.; Li, Kun; Su, Yonghua; Yang, Yinxue; Upton, Zee
• Is Part Of: Chemico-biological interactions. Volume 228(2015)
• Page Start: 18
• Page End: 27
• Publication Date: 2015-02-25
• Subjects: αSMA alpha-smooth muscle actin -- Bcl-2 B-cell lymphoma 2 -- Caspases Cysteine-dependent aspartate-directed proteases -- COL1A1 collagen type І gene -- COL3A1 collagen type Ш gene -- DAPI 4′, 6-diamidino-2-phenylindole -- DMEM Dulbecco's Modified Eagle's Medium -- DMSO dimethyl sulfoxide -- Erk1/2 extracellular signal-regulated kinase 1 and 2 -- FCS fetal calf serum -- HSF hypertrophic scar-derived human skin fibroblasts -- JNK1/2 c-Jun N-terminal kinase 1 and 2 -- KC human skin keratinocytes -- NaOH sodium hydroxide -- p38α/β mitogen-activated protein kinase 14 α and β -- p-p38α/β phospho-p38 α and β -- p-Erk1/2 phospho-Erk 1 and 2 -- qRT-PCR quantitative reverse transcriptase polymerase chain reaction -- SDS–PAGE Sodium dodecyl sulphate polyacrylamide gel electrophoresis -- SEM standard error of the mean -- SFM serum free medium -- TUNEL Terminal deoxynucleotidyl Transferase dUTP nick end labelling; Scar remediation therapy -- Apoptosis -- Collagen reduction -- Shikonin; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2014.12.037
• Languages: English
• ISSNs: 0009-2797

Abstract

Highlights: Shikonin decreases hypertrophic scar-derived human fibroblasts proliferation. Shikonin inhibits collagen production in hypertrophic scar-derived human fibroblasts. Shikonin induces hypertrophic scar-derived human skin fibroblasts apoptosis. Shikonin differentially regulates apoptosis related protein expression. Shikonin down-regulates collagen production related gene expression. Abstract: Scarring is a significant medical burden; financially to the health care system and physically and psychologically for patients. Importantly, there have been numerous case reports describing the occurrence of cancer in burn scars. Currently available therapies are not satisfactory due to their undesirable side-effects, complex delivery routes, requirements for long-term use and/or expense. Radix Arnebiae ( Zi Cao ), a perennial herb, has been clinically applied to treat burns and manage scars for thousands of years in Asia. Shikonin, an active component extracted from Radix Arnebiae, has been demonstrated to induce apoptosis in cancer cells. Apoptosis is an essential process during scar tissue remodelling. It was therefore hypothesized that Shikonin may induce apoptosis in scar-associated cells. This investigation presents the first detailed in vitro study examining the functional responses of scar-associated cells to Shikonin, and investigates the mechanisms underlying these responses. The data obtained suggests that Shikonin inhibits cell viability and proliferation and reduces detectable collagen in scar-derived fibroblasts. Further investigation revealed that Shikonin induces apoptosis in scar fibroblasts by differentially regulating the expression of caspase 3, Bcl-2, phospho-Erk1/2 and phospho-p38. In addition, Shikonin down-regulates the expression of collagen I, collagen III and alpha-smooth muscle actin genes hence attenuating collagen synthesis in scar-derived fibroblasts. In summary, it is demonstrated that Shikonin induces apoptosis and decreases collagen production in scar-associated fibroblasts and may therefore hold potential as a novel scar remediation therapy.