title: Resveratrol exerts growth inhibitory effects on human SZ95 sebocytes through the inactivation of the PI3-K/Akt pathway.
abstract: 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.
authors: Major in Biomedical Science, Department of Medicine, Chung‑Ang University, Seoul 156‑756, Republic of Korea.
authors: So Young
authors: SY
authors: Kim
authors: Department of Dermatology, Chung‑Ang University College of Medicine, Seoul 156‑756, Republic of Korea.
authors: Moo Yeol
authors: MY
authors: Hyun
authors: Major in Biomedical Science, Department of Medicine, Chung‑Ang University, Seoul 156‑756, Republic of Korea.
authors: Kyung Chan
authors: KC
authors: Go
authors: Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau 06847, Germany.
authors: Christos C
authors: CC
authors: Zouboulis
authors: Major in Biomedical Science, Department of Medicine, Chung‑Ang University, Seoul 156‑756, Republic of Korea.
authors: Beom Joon
authors: BJ
authors: Kim
mesh_terms: D002461:Cell Line, Transformed; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D050155:Lipogenesis / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000077185:Resveratrol; D012627:Sebaceous Glands / Q000166:cytology*; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D002867:Chromones; D005419:Flavonoids; D009025:Morpholines; D013267:Stilbenes; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D000077185:Resveratrol; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one