Antiproliferative, Proapoptotic, And Potential Antifibrotic Effects Of α-Mangostin In Fibroblasts From Keloid Lesions And Normal Skin
Abstract
Keloids are disfiguring lesions that result from an abnormal wound healing process. Despite the availability of numerous therapeutic options, keloids remain challenging to treat and often recur after therapy. α-Mangostin, a natural xanthone isolated from the fruit of the Mangosteen tree, has been used for centuries in many Southeast Asian nations for medicinal purposes, and has gained attention more recently due to its anti-inflammatory, antimicrobial, and antioxidant properties, with numerous studies suggesting possible anticarcinogenic activities. Hypothetically, α-mangostin may have therapeutic value for keloid suppression. To investigate this hypothesis, the effects of α-mangostin on fibroblast proliferation, apoptosis, and gene expression in vitro were analyzed. Dermal fibroblasts were isolated and cultured from normal human skin and excised keloid lesions (3 donors each), and were treated with multiple doses of α-mangostin in vitro. Dose-dependent decreases in proliferation in keloid and normal fibroblasts were observed following treatment with α-mangostin. The α-mangostin treated fibroblasts displayed significantly increased expression of C/EBP homologous protein (CHOP), which mediates endoplasmic reticulum stress-induced apoptosis, suggesting increased apoptosis. In addition, numerous changes in gene expression were observed in α-mangostin-treated keloid fibroblasts, including decreased expression of collagen type I alpha 1 chain (COL1A1) and increased expression of matrix metalloproteinase 1 (MMP1), MMP3, and MMP13. Secretion of pro-collagen I was decreased, and secretion of MMP1 and MMP3 were increased, in α-mangostintreated fibroblasts. The results suggest that α-mangostin may exhibit antiproliferative, proapoptotic, and antifibrotic activities in keloid and normal fibroblasts. Thus, this study suggests that further investigation is warranted to fully explore the therapeutic potential of α-mangostin for suppression of keloid development.