Resveratrol-sensitized UVA induced apoptosis in human keratinocytes through mitochondrial oxidative stress and pore opening

Abstract

Resveratrol (3, 5, 4′-trihydroxy- trans- stilbene), a polyphenol compound, is derived from natural products such as the skin of red grapes, blueberries and cranberries. Resveratrol not only exhibits antioxidant, cardioprotection, and anti-aging properties, but can also inhibit cancer cell growth and induce apoptosis. It has been shown that resveratrol inhibits the activation of Nf-kB and subsequently down regulates the expression of Nf-kB regulated genes such as interleukin-2 and Bcl-2, leading to cell cycle arrest and increased apoptosis in multiple myeloma cells. In the skin, resveratrol has been reported to sensitize keratinocytes to UVA induced apoptosis. However, the effect of resveratrol on opening of the mitochondrial permeability transition pore has not been previously examined. Our data show that UVA (14J/cm2) along with resveratrol causes massive oxidative stress in mitochondria. As a consequence of oxidative stress, the mitochondrial membrane potential decreases which results in opening of the mitochondrial pores ultimately leading to apoptosis in human keratinocytes. These results may have clinical implications for development of future chemotherapeutic treatment for tumors of the skin.

Pterostilbene Inhibits Human Multiple Myeloma Cells via ERK1/2 and JNK Pathway In Vitro and In Vivo

“…Resveratrol is a natural compound found in grapes, blueberries and cranberries, which has been reported to have anti-tumor properties due to its ability to induce apoptosis and cell cycle arrest [5]. Previous work has confirmed that resveratrol can inhibit the proliferation of human MM cell lines and alter the population of S phase [6].…”

Unifying Mechanism for Nutrients as Anticancer Agents: Electron Transfer, Reactive Oxygen Species and Oxidative Stress

“…The combination of RSV and arsenite increased apoptotic cancer cell death through generation of OS. A report deals with OS in eye cells of diabetic rats involving an increase in OS (Boyer, Jandova, Janda et al, 2012). Protein carbonyl content was increased and GSH levels were decreased.…”

Effects of UV-A LED light irradiation on growth of cultured RAW 264.7 cells

“…Exposure of skin to UV-A generates large quantities of intracellular ROS, which directly or indirectly affect various cell signaling pathways, including oxidative stress and apoptosis (Fu et al 2000). In addition, oxidative stress mediates various UV-induced cutaneous reactions, including inflammation, photosensitivity, and carcinogenesis (Boyer et al 2012;Narayanapillai et al 2012). These effects attributed to UV-A irradiation are also associated with generation of ROS including singlet oxygen ( 1 O 2 ), superoxide radicals (O 2 ¡ ), hydrogen peroxide (H 2 O 2 ), hydroxyl radicals (OH), and nitric oxide (NO), and these ROS were found to induce various biological processes, including apoptosis or programmed cell death such as mitochondrial oxidative stress (Boyer et al 2012) or DNA damage (Hseu et al 2012).…”

“…In addition, oxidative stress mediates various UV-induced cutaneous reactions, including inflammation, photosensitivity, and carcinogenesis (Boyer et al 2012;Narayanapillai et al 2012). These effects attributed to UV-A irradiation are also associated with generation of ROS including singlet oxygen ( 1 O 2 ), superoxide radicals (O 2 ¡ ), hydrogen peroxide (H 2 O 2 ), hydroxyl radicals (OH), and nitric oxide (NO), and these ROS were found to induce various biological processes, including apoptosis or programmed cell death such as mitochondrial oxidative stress (Boyer et al 2012) or DNA damage (Hseu et al 2012). ROS were induced by UV photo-irradiation of some photosensitizers in a medium containing fatty acids and vitamins (Regensburger et al 2012) and cytoplasmic urocanic acid, riboflavin, and b-nicotinamide adenine dinucleotide (NAD) (Baier et al 2006).…”