title: Silibinin is a potent sensitizer of UVA radiation-induced oxidative stress and apoptosis in human keratinocyte HaCaT cells.
abstract: UVA radiation (315-400 nm), which constitutes ca 95% of the UV irradiation in natural sunlight reaching earth surface, is a major environmental risk factor associated with human skin cancer pathogenesis. UVA is an oxidizing agent that causes significant damage to cellular components through the release of reactive oxygen species (ROS) and leads to photoaging and photocarcinogenesis. Here we investigate the effect of silibinin, the flavonolignan from Silybum marianum, on UVA-induced ROS and cell death in human keratinocyte cell line HaCaT. In addition, the effect of silibinin on UVA-induced intracellular ROS-mediated endoplasmic reticulum (ER) stress was also analyzed. UVA irradiation resulted in ROS production and apoptosis in HaCaT cells in a dose-dependent manner, and the ROS levels and apoptotic index were found to be elevated significantly when the cells were treated with 75 μmsilibinin for 2 h before UVA exposure. When the cells were pretreated with 10 mmN-acetyl cysteine, the enhancement of UVA-induced apoptosis by silibinin was compromised. Furthermore, we found that silibinin enhances ER stress-mediated apoptosis in HaCaT cells by increasing the expression of CHOP protein. These results suggest that silibinin may be beneficial in the removal of UVA-damaged cells and the prevention of skin cancer.
authors: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO, USA.
authors: Sreekanth
authors: S
authors: Narayanapillai
authors: Chapla
authors: C
authors: Agarwal
authors: Cynthia
authors: C
authors: Tilley
authors: Rajesh
authors: R
authors: Agarwal
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000528:radiation effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000528:radiation effects; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D020944:Silybum marianum / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D017319:Photosensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D051742:Transcription Factor CHOP / Q000819:agonists / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D000975:Antioxidants; C497249:DDIT3 protein, human; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D012838:Silymarin; D051742:Transcription Factor CHOP; D000077385:Silybin; D000111:Acetylcysteine