The effect of 5α-oleandrin on keloid fibroblast activities

Abstract

BackgroundKeloids develop due to hyperactivity of keloid fibroblast (KF) in proliferation, migration, and collagen deposition along with low rates of collagen degradation. These are a result of the Wnt/β catenin signaling pathways under stimulation of TGF-β. 5α-oleandrin can suppress Wnt-targeted genes of osteosarcoma cells. We aimed to evaluate the anti-fibrotic effects of 5α-oleandrin on KF activities.MethodsWe collected the core of keloid materials from six patients who underwent keloid debulking surgery. Passage 4 of KF cells were then treated with mitomycin-C, 5α-oleandrin, and dilution medium as the negative control. To determine the effective dose of 5α-oleandrin, we diluted 5α-oleandrin into various concentrations. The incubation periods were 24 h, 48 h, and 72 h. The anti-proliferation and anti-fibrotic properties were measured using standard assay.ResultsBoth the mitomycin-C and 5α-oleandrin treated groups indicated decrease in proliferation index (86.16 ± 4.20% and 73.76 ± 4.94%, respectively), collagen deposition index (90.26 ± 1.72% and 71.35 ± 4.26%, respectively), and migration capacity (33.51 ± 1.50% and 28.57 ± 1.58%, respectively). These were significant changes (p ≤ 0.05) compared to the non-treated group. Antifibrotic activities of 5α-oleandrin in cellular proliferation and collagen deposition were better than mitomycin-C.ConclusionsThe 5α-oleandrin has good antifibrotic effect in keloid fibroblast activities.

Ethanolic Extract of Nerium indicum Mill. Decreases Transforming Growth Factor Beta-1 and Vascular Endothelial Growth Factor Expressions in Keloid Fibroblasts

“…In this study, the VEGF-A expression of keloid fibroblasts was measured at the concentration of N. indicum 2 µg/ml and 1 µg/ml extract and showed a significantly lower level compared to the control medium (p < 0.05). This finding is in accordance with the research of Wahyuningsih et al in 2018 that found ethanolic extract of N. indicum can inhibit the proliferation of keloid fibroblasts for a 48-h incubation period [8]. In another study, the administration of taginin VEGF-A expression of keloid fibroblasts at the concentration of N. indicum 2 µg/ml and 1 µg/ml extract showed a significantly lower VEGF-A level compared to the medium control (p < 0.05).…”

“…A significant decrease in keloid fibroblast TGF-β1 levels occurred at all of the N. indicum extract concentrations (2 µg/ml, 1 µg/ml, and 0.5 µg/ml) compared to those in the control group (p < 0.05). This is in accordance with previous studies by Dachlan (2019) that showed 5α-oleandrin isolates from ethanol extraction of N. indicum leaves significantly decreased TGF-β1 expression compared to control medium (p < 0.05) [8]. Increased TGF-β1 activity in fibroblast cells can enlarge the ability to stimulate tissue remodeling and the excessive process of wound healing causes keloid tissue.…”

“…Oleandrin cytotoxicity (IC 50 15.6 nM) was greater than doxorubicin (IC 50 26.9 nM) and cisplatin (IC 50 79.8 nM) on M19 cell line (melanoma) [6], [7]. 5α-oleandrin has antikeloid activity by inhibiting keloid fibroblast proliferation, fibroblast migration, collagen deposition, and TGF-β1 synthesis [8]. Ethanolic extract N. indicum inhibits proliferation of keloid fibroblasts with IC 50 0.458 µg/ml, also can inhibit collagen deposit with IC 50 0.055 µg/ml at 72 h incubation period.…”