title: Functional and mechanistic investigation of Shikonin in scarring.
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.
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia; Tissue Organ Bank & Tissue Engineering Centre, General Hospital of Ningxia Medical University, Ningxia, China. Electronic address: y2.xie@qut.edu.au.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia.
authors.forename: Chen
authors.initials: C
authors.lastname: Fan
authors.affiliation: Cancer Research Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia.
authors.forename: Ying
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia.
authors.forename: Emily
authors.initials: E
authors.lastname: Lynam
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia; Tissue Organ Bank & Tissue Engineering Centre, General Hospital of Ningxia Medical University, Ningxia, China.
authors.forename: David I
authors.initials: DI
authors.lastname: Leavesley
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia.
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.affiliation: Changhai Hospital of Traditional Chinese Medicine, Second Military Medical University, Shanghai, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Su
authors.affiliation: Tissue Organ Bank & Tissue Engineering Centre, General Hospital of Ningxia Medical University, Ningxia, China.
authors.forename: Yinxue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia.
authors.forename: Zee
authors.initials: Z
authors.lastname: Upton
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002921:Cicatrix / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects; D009285:Naphthoquinones / Q000494:pharmacology* / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D009285:Naphthoquinones; C016101:shikonin; D003094:Collagen
keywords: Apoptosis; Collagen reduction; Scar remediation therapy; Shikonin