Abstract
Ultraviolet (UV) radiation–induced skin damage contributes strongly to the formation of melanoma, a highly lethal form of skin cancer. Quercetin (Qu), the most widely consumed dietary bioflavonoid and well known inhibitor of phosphoinositide 3-kinase (PI3K) and mitogen activated protein (MAP) kinase signalling, has been reported to be chemopreventive in several forms of non-melanoma skin cancers. Here, we report that the treatment of ultraviolet (UV)-B-irradiated B16F10 melanoma cells with quercetin resulted in a dose dependent reduction in cell viability and increased apoptosis. The present study has brought out that the pro-apoptotic effects of quercetin in UVB-irradiated B16F10 cells are mediated through the elevation of intracellular reactive oxygen species (ROS) formation, calcium homeostasis imbalance, modulation of anti-oxidant defence response and depolarization of mitochondrial membrane potential (ΔΨM). Promotion of UVB-induced cell death by quercetin was further revealed by cleavage of chromosomal DNA, caspase activation, poly (ADP) ribose polymerase (PARP) cleavage, and an increase in sub-G1 cells. Quercetin markedly attenuated MEK-ERK signalling, influenced PI3K/Akt pathway, and potentially enhanced the UVB-induced NF-κB nuclear translocation. Furthermore, combined UVB and quercetin treatment decreased the ratio of Bcl-2 to that of Bax, and upregulated the expression of Bim and apoptosis inducing factor (AIF). Overall, these results suggest the possibility of using quercetin in combination with UVB as a possible treatment option for melanoma in future.
Highlights
Melanoma arises from the malignant transformation of melanocytes, the pigment producing cells of skin
We found that the treatment of UVB-irradiated B16F10 cells with 5, 10, 20, and 40 μM quercetin increased the percentage of cell death to around 61%, 65%, 72% and 74% respectively (Fig 1G)
We studied the key effects of quercetin in UVB–irradiated A375 human melanoma cells
Summary
Melanoma arises from the malignant transformation of melanocytes, the pigment producing cells of skin. Ultraviolet radiation, in particular UVB (λ, 290–320 nm) is known to alter cellular functions via DNA damage, activation of death receptors, depletion of anti-oxidant defences, generation of reactive oxygen species (ROS), and the resultant alterations in a large variety of signalling events [6]. Other signalling pathways documented to play an important role in the response of cells to UVB-irradiation include Ras-Raf-MEK-ERK pathway and phosphatidylinositol-3-kinase (PI3K)/Akt survival signals. In addition to these signalling molecules, C-Jun N-terminal kinase (JNK) and p-38 subgroups of mitogen-activated protein kinases have been suggested to play critical role in apoptosis, cell proliferation, and/or differentiation [16, 17]
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