Abstract
Curcumin—a rhizomal phytochemical from the plant Curcuma longa—is well known to inhibit cell proliferation and to induce apoptosis in a broad range of cell lines. In previous studies we showed that combining low curcumin concentrations and subsequent ultraviolet A radiation (UVA) or VIS irradiation induced anti-proliferative and pro-apoptotic effects. There is still debate whether curcumin induces apoptosis via the extrinsic or the intrinsic pathway. To address this question, we investigated in three epithelial cell lines (HaCaT, A431, A549) whether the death receptors CD95, tumor necrosis factor (TNF)-receptor I and II are involved in apoptosis induced by light and curcumin. Cells were incubated with 0.25–0.5 µg/mL curcumin followed by irradiation with 1 J/cm2 UVA. This treatment was combined with inhibitors specific for distinct membrane-bound death receptors. After 24 h apoptosis induction was monitored by quantitative determination of cytoplasmic histone-associated-DNA-fragments. Validation of our test system showed that apoptosis induced by CH11 and TNF-α could be completely inhibited by their respective antagonists. Interestingly, apoptosis induced by curcumin/light treatment was reversed by none of the herein examined death receptor antagonists. These results indicate a mechanism of action independent from classical death receptors speaking for intrinsic activation of apoptosis. It could be speculated that a shift in cellular redox balance might prompt the pro-apoptotic processes.
Highlights
Phytochemicals have a crucial role in drug discovery and development [1,2]
There are contradictory observations concerning the mode of apoptosis induction by curcumin
Intrinsic apoptosis induction was observed in mamma carcinoma cells as well as in HL-60 and kidney carcinoma cells [21,34,35,36,37]
Summary
Curcumin has been a part of traditional Asian medicine for thousands of years due to its extensive effects on cell physiology. It can be isolated from the rhizome of the ginger plant Curcuma longa. Reducing the proliferative potential of neoblastic cells as well as inducing pro-apoptotic effects is the mode of choice to target cancer cells [6,18]. These two criteria can be addressed by curcumin. Characteristic of apoptosis induction via the extrinsic pathway is the binding of extracellular ligands to transmembrane death receptors, e.g., CD95 or tumor necrosis factor (TNIntF. )J.-αMorl.eSccei.p2t0o1r9s, 2. 0R, xeFcOepRtPoErEcRluREstVeIrEiWng, binding with homologous trimeric ligands and recrui2tmofen12t of cytoplasmic adaptor proteins leads to auto-catalytic activation of pro-caspase-8 [23,24]
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