A novel antioxidant 3-O-Caffeoyl-1-methylquinic acid enhances ultraviolet A-mediated apoptosis in immortalized HaCaT keratinocytes via Sp1-dependent transcriptional activation of p21WAF1/Cip1

Abstract

It has become clear that ultraviolet A (UVA) radiation from the solar spectrum is a major environmental challenge to the skin. This necessitates developing novel mechanism-based agents capable of ameliorating UVAinduced effects in the skin. We recently described a novel antioxidant, 3-O-Caffeoyl-1-methylquinic acid (MCGA3) from leaves of bamboo. Here, we investigated the photochemopreventive effects of MCGA3 against UVAmediated apoptosis in immortalized HaCaT keratinocytes. Pretreatment of MCGA3 rendered cells more sensitive to subsequent UVA irradiation-induced apoptosis as well as completely reversed UVA-induced sustained phosphorylation of extracellular signal-regulated kinase 1/2 and protein kinase Ca, downregulation of p21, and reactive oxygen species generation. Interestingly, MCGA3 itself effectively induced p21 protein and mRNA levels. Silencing of p21 by RNA interference revealed a pivotal role of p21 in generating G 1 -S arrest and in enhancing UVA-mediated apoptosis. Transcriptional activation of p21 by MCGA3 was mediated through the proximal region of multiple Sp1 sites regardless of p53-binding site in p21 promoter, and this effect was augmented by desferroioxamine, an iron chelating agent. Additional studies suggested that iron chelation-driven hypoxia by MCGA3 may function in activation of p21. MCGA3 could be a useful agent to prevent photocarcinogenesis via apoptotic elimination of p53 mutant and DNA-repair defective cells caused by UVA radiation.

Green tea catechins alone or in combination alter functional parameters of human neutrophils via suppressing the activation of TLR-4/NFκB p65 signal pathway

“…However, several studies indicate (Chen et al, 2000;Kweon et al, 2007;Lee-Hilz et al, 2006;Shen et al, 2005)that catechins induce an upregulation of antioxidant and detoxifying enzymes via Nrf2 pathway activation. Nrf2 is a transcription factor that regulates the expression of numerous detoxifying and antioxidants enzymes.…”

Potential medicinal application and toxicity evaluation of extracts from bamboo plants

“…(2) Prevented photocarcinogenesis via apoptotic elimination of p53 mutant and DNA-repair defective cells. (3) Induced Nrf2dependent phase II detoxifying genes and altered intracellular glutathione redox Kweon et al (2004), Kweon et al (2007) and Kweon et al (2006) Butanol fraction of leaves; chlorogenic acid derivatives Cell-free assay Antioxidant activity Kweon et al (2001) 250 and 500 mg/kg in drinking water, days 1-9 or 18-20 of pregnancy, extract-free water as control.…”

“…This compound was found to upregulate the expression of heme oxygenase-1 (HO-1) and other Nrf2-dependent phase II detoxifying genes, and protect against peroxideinduced cytotoxicity (Kweon et al, 2004;Kweon et al, 2006). This compound also prevents photocarcinogenesis via apoptotic elimination of tumor protein 53 (p53) mutant and DNA-repair defective cells (Kweon et al, 2007).…”

The ETS Family Transcription Factor ELK-1 Regulates Induction of the Cell Cycle-regulatory Gene p21 and the BAX Gene in Sodium Arsenite-exposed Human Keratinocyte HaCaT Cells

“…Although the mechanisms of p21 apoptotic regulation are poorly understood, p21 can promote apoptosis under certain circumstances (70,71). For example, p21 overexpression enhances cisplatin-induced cell death in ovarian carcinoma cells (72), and the silencing of p21 by RNAi in HaCaT cells indicates that p21 functions in UVA-induced apoptosis and the G 1 /S phase cell cycle arrest (73). Thus, we suggest that the accumulation of p21 may play an important role in NaASO 2 -induced cytotoxicity through cell cycle dysregulation and apoptosis in HaCaT cells.…”