Anti‐apoptotic effects of curcumin on photosensitized human epidermal carcinoma A431 cells

Abstract

Photodynamic treatment (PDT) can elicit a diverse range of cellular responses, including apoptotic cell death. Previously, we showed that PDT stimulates caspase-3 activation and subsequent cleavage and activation of p21-activated kinase 2 (PAK2) in human epidermal carcinoma A431 cells. Curcumin, the yellow pigment of Curcuma longa, is known to have anti-oxidant and anti-inflammatory properties. In the present study, using Rose Bengal (RB) as the photosensitizer, we investigated the effect of curcumin on PDT-induced apoptotic events in human epidermal carcinoma A431 cells. We report that curcumin prevented PDT-induced JNK activation, mitochondrial release of cytochrome c, caspase-3 activation, and cleavage of PAK2. Using the cell permeable dye DCF-DA as an indicator of reactive oxygen species (ROS) generation, we found that both curcumin and ROS scavengers (i.e., l-histidine, a-tocopherol, mannitol) abolished PDT-stimulated intracellular oxidative stress. Moreover, all these PDT-induced apoptotic changes in cells could be blocked by singlet oxygen scavengers (i.e., l-histidine, a-tocopherol), but were not affected by the hydroxyl radical scavenger mannitol. In addition, we found that SP600125, a JNK-specific inhibitor, reduced PDT-induced JNK activation as well as caspase-3 activation, indicating that JNK activity is required for PDT-induced caspase activation. Collectively, these results demonstrate that singlet oxygen triggers JNK activation, cytochrome c release, caspase activation and subsequent apoptotic biochemical changes during PDT and show that curcumin is a potent inhibitor for this process.

Pharmacokinetics and Pharmacodynamics of Curcumin

“…8 Systematic preclinical safety studies orchestrated by the US National Cancer Institute (NCI) did not discover any adverse effects in rats, dogs, or monkeys at doses of up to 3.5 g/kg administered up to 3 months in duration. 24 One early report suggested a potentially ulcerogenic effect of dietary curcumin in the stomach of the albino rat, 67 but this finding has not been replicated in subsequent rodent studies. In more recent preclinical investigations of dietary curcumin, toxicity has not been observed at 2% of the diet in rats 16 (approximately 1.2 g/kg) or at 0.2% of the diet in mice 31 (approximately 300 mg/kg).…”

Citrinin induces apoptosis via a mitochondria-dependent pathway and inhibition of survival signals in embryonic stem cells, and causes developmental injury in blastocysts

“…have not yet been clearly defined, studies have shown that caspase activation, MMP (mitochondrial membrane potential) changes and JNK (c-Jun N-terminal kinase) activation are critical for the mitochondria-dependent apoptotic pathway [9,14]. In addition, previous studies have shown that some apoptotic stimuli trigger heat-shock responses, such as activation of the HSPs (heat-shock proteins), which are molecular chaperones that rescue damaged proteins by facilitating their refolding [15,16].…”

Investigation of curcumin-mediated signalling pathways in head and neck squamous cell carcinoma

“…Curcumin is shown to affect the phosphorylation of MAPK1/3 and also reported to regulate the cleavage and activation of p21 (RAC1)-activated kinase 2 (PAK2). 10,[24][25][26] In addition, curcumin has also been reported to affect the autophosphorylation of epidermal growth factor receptor (EGFR) where it has also been shown to decrease phosphorylation of EGFR. 27,28 Our group has studied dysregulation in tyrosine kinases in the same cell line, Cal 27, in response to curcumin.…”