Calcipotriol is a synthetic vitamin D3 analog with high affinity for vitamin D receptors[1]. Calcipotriol is mainly used to treat psoriasis. It is also effective in certain keratotic diseases (ichthyosis) as well as localized scleroderma and vitiligo, and has important immunomodulatory functions [2].
In vitro, calcipotriol (10nM) treated HL-60 cells for 24h caused cell apoptosis, but caused cell differentiation at a higher dose (100nM)[3]. Calcipotriol (0.001-10μM) treated SCC13 cells for 4 days, dose-dependently inhibited cell proliferation and stimulated cell differentiation, but did not induce SCC13 cell apoptosis, and specifically inhibited the autocrine activation of the EGFR signaling pathway [4].
In vivo, calcipotriol combined with BDP ointment (40 mg, once daily, administered topically on the skin) treated rats with psoriasis-like dermatitis. Compared with the vaseline treatment group, it significantly inhibited ear skin thickening and Transepidermal water loss[5]. Calcipotriol (0.1mg/kg) can reduce knee joint swelling and relieve synovitis through a single intra-articular injection in ZIA rats [6].
References:
[1] Sakabe J, et al. Calcipotriol increases hCAP18 mRNA expression but inhibits extracellular LL37 peptide production in IL-17/IL-22-stimulated normal human epidermal keratinocytes[J].Acta Dermato-Venereologica, 2014, 94(5).
[2] Guilhou JJ. Le Calcipotriol [Calcipotriol]. Ann Dermatol Venereol. 2001 Mar;128(3 Pt 1):229-37. French. PMID: 11319386.
[3] Milczarek M, Chodyński M, Filip-Psurska B, et al. Synthesis and biological activity of diastereomeric and geometric analogs of calcipotriol, PRI-2202 and PRI-2205, against human HL-60 leukemia and MCF-7 breast cancer cells[J]. Cancers, 2013, 5(4): 1355-1378.
[4] Lee E A, Jeon S H, Yi J Y, et al. Calcipotriol inhibits autocrine phosphorylation of EGF receptor in a calcium-dependent manner, a possible mechanism for its inhibition of cell proliferation and stimulation of cell differentiation[J]. Biochemical and biophysical research communications, 2001, 284(2): 419-425.
[5] Satake K, Amano T, Okamoto T. Low systemic exposure and calcemic effect of calcipotriol/betamethasone ointment in rats with imiquimod-induced psoriasis-like dermatitis[J]. European Journal of Pharmacology, 2018, 826: 31-38.
[6] Huhtakangas J A, Huovinen J, Laaksonen S, et al. A single intra-articular dose of vitamin D analog calcipotriol alleviates synovitis without adverse effects in rats[J]. Plos one, 2021, 16(4): e0250352.
卡泊三醇(Calcipotriol)是一种合成的维生素D3 类似物,对维生素D受体具有高亲和力[1]。卡泊三醇主要用于治疗银屑病,对某些角化性疾病(鱼鳞病)以及局部硬皮病和白癜风也有效,并具有重要的免疫调节功能[2]。
在体外,卡泊三醇(10nM)处理HL-60细胞24h,引起细胞凋亡,但在更高剂量(100nM)时引起细胞分化[3]。卡泊三醇(0.001-10µM)处理SCC13细胞4天,剂量依赖性地抑制细胞增殖并刺激细胞分化,但不诱导SCC13细胞凋亡,且特异性地抑制了EGFR信号通路的自分泌激活[4]。
在体内,卡泊三醇联合BDP软膏(40mg,每日一次,给药方式为皮肤局部涂抹)治疗银屑病样皮炎大鼠,与凡士林治疗组相比,显著抑制了耳部皮肤增厚和经皮水分流失[5]。卡泊三醇(0.1 mg/kg)通过单次关节内注射治疗ZIA大鼠,可以减轻膝关节肿胀,缓解滑膜炎[6]。