Kim So Young, Hyun Moo Yeol, Go Kyung Chan, Zouboulis Christos C, Kim Beom Joon
Major in Biomedical Science, Department of Medicine, Chung‑Ang University, Seoul 156‑756, Republic of Korea.
Department of Dermatology, Chung‑Ang University College of Medicine, Seoul 156‑756, Republic of Korea.
Int J Mol Med. 2015 Apr;35(4):1042-50. doi: 10.3892/ijmm.2015.2098. Epub 2015 Feb 12.
Resveratrol is known to be a naturally produced polyphenol that is able to reduce cell proliferation in several types of cancer cells and adipocytes. However, the antiproliferative effects of resveratrol on the growth of human sebocytes are not yet clear. In the present study, we investigated possible cellular pathways associated with these growth inhibitory effects on human SZ95 sebocytes. Our results revealed that resveratrol inhibited the proliferation of sebocytes, and that this resulted in disruption of the cell cycle. The inactivation of extracellular signal-regulated protein kinase (ERK), Akt and peroxisome proliferator-activated receptor (PPAR)-γ was also shown to be involved in the inhibition of sebocyte growth by resveratrol. To examine the antiproliferative effects of resveratrol, we determined the levels of cell cycle control proteins. Resveratrol inhibited cyclin D1 synthesis, whereas it stimulated p21WAF1/CIP1 (p21) and p27KIP1 (p27) synthesis. In addition, we demonstrated that the resveratrol-mediated cell cycle arrest resulted in an increase in the proportion of cells in the sub-G0/G1 phase. Moreover, we found that the growth inhibitory effects of resveratrol were enhanced by treatment with LY294002 [a phosphatidylinositol 3-kinase (PI3-K) inhibitor] more so than by treatment with PD98059 (a MEK inhibitor), which indicates that resveratrol exerts its inhibitory effects on sebocyte proliferation through the inhibition of Akt. Linoleic acid (LA) is a well-established lipid inducer in sebocytes and is known to stimulate sebocyte differentiation through the upregulation of PPAR-γ. In this study, resveratrol was found to decrease the lipid content and PPAR-γ expression during LA-stimulated lipogenesis. Our results indicate that resveratrol plays a critical role in the inhibition of sebocyte growth through the inactivation of the Akt pathway. The present data suggest that resveratrol may be used as a therapeutic agent for the treatment of acne vulgaris.
白藜芦醇是一种天然产生的多酚，已知它能够减少多种癌细胞和脂肪细胞的增殖。然而，白藜芦醇对人皮脂腺细胞生长的抗增殖作用尚不清楚。在本研究中，我们调查了与白藜芦醇对人SZ95皮脂腺细胞生长抑制作用相关的可能细胞途径。我们的结果显示，白藜芦醇抑制皮脂腺细胞增殖，并导致细胞周期紊乱。细胞外信号调节蛋白激酶（ERK）、Akt和过氧化物酶体增殖物激活受体（PPAR）-γ的失活也被证明与白藜芦醇对皮脂腺细胞生长的抑制有关。为了研究白藜芦醇的抗增殖作用，我们测定了细胞周期调控蛋白的水平。白藜芦醇抑制细胞周期蛋白D1的合成，而刺激p21WAF1/CIP1（p21）和p27KIP1（p27）的合成。此外，我们证明白藜芦醇介导的细胞周期阻滞导致亚G0/G1期细胞比例增加。而且，我们发现用LY294002（一种磷脂酰肌醇3激酶（PI3-K）抑制剂）处理比用PD98059（一种MEK抑制剂）处理更能增强白藜芦醇的生长抑制作用，这表明白藜芦醇通过抑制Akt对皮脂腺细胞增殖发挥抑制作用。亚油酸（LA）是皮脂腺中一种公认的脂质诱导剂，已知它通过上调PPAR-γ刺激皮脂腺细胞分化。在本研究中，发现白藜芦醇在LA刺激的脂肪生成过程中降低脂质含量和PPAR-γ表达。我们的结果表明，白藜芦醇通过Akt途径失活在抑制皮脂腺细胞生长中起关键作用。目前的数据表明，白藜芦醇可能用作治疗寻常痤疮的治疗剂。
