Malignant melanoma is the deadliest
skin cancer, due to its propensity to metastasize. MAPKs and NF-κB pathways are constitutively activated in
melanoma and promote cell proliferation, cell invasion,
metastasis formation, and resistance to therapeutic regimens. Thus, they represent potential targets for
melanoma prevention and treatment.
Phytochemicals are gaining considerable attention for the management of
melanoma because of their several cellular and molecular targets. A screening of a small library of
sesquiterpenes lactones selected
cynaropicrin, isolated from the aerial parts of Centaurea drabifolia subsp. detonsa, for its potential anticancer effect against
melanoma cells. Treatment of human
melanoma cells A375 with
cynaropicrin resulted in inhibition of cell proliferation and induction of caspase-3-dependent apoptosis. Furthermore,
cynaropicrin reduced several cellular malignant features such migration, invasion, and colonies formation through the inhibition of ERK1/2 and NF-κB activity.
Cynaropicrin was able to reduce intracellular
reactive oxygen species generation, which are involved in all the stages of
carcinogenesis. Indeed,
cynaropicrin increased the expression of several
antioxidant genes, such as
glutamate-cysteine ligase and
heme oxygenase-1, by promoting the activation of the
transcription factor Nrf-2. In conclusion, our results individuate
cynaropicrin as a potential adjuvant chemotherapeutic agent for
melanoma by targeting several protumorigenic signaling pathways.