Cedrus atlantica extract inhibits melanoma progression by suppressing epithelial-mesenchymal transition and inducing mitochondria-mediated apoptosis.

Abstract

Melanoma has a low incidence, accounting for less than 5% of skin cancers; however, it is the most lethal cancer, primarily because of its high potential for metastasis and resistance to different treatments. Natural products can sensitize melanoma to chemotherapy and overcome drug resistance. Previous studies have reported Cedrus atlantica extract has various pharmacological benefits such as anti-inflammatory, antioxidant, antibacterial, and analgesic properties. This study aimed to explore the effects of C. atlantica extract (CAt) against melanoma in vitro and in vivo. The effects of CAt on B16F10 cell viability, proliferation, migration, invasion, and apoptosis were detected using MTT, colony formation, wound-healing, Boyden chamber, and TUNEL assays. Semi-quantitative RT-PCR and western blotting were used to measure mRNA and protein expression, respectively. Results revealed that CAt selectively decreased the viability of B16F10 cells and inhibited colony formation in a dose-dependent manner. CAt reduces cell migration and invasion by regulating epithelial-mesenchymal transition-associated proteins (Snail, E-cadherin, and vimentin). Moreover, CAt enhanced the Bax/Bcl-2 ratio and the expression of cleaved-caspase-9, caspase-3, and PARP1, resulting in the activation of mitochondria-mediated apoptosis. In an in vivo study, CAt significantly inhibited tumor growth and prolonged the lifespan of mice at a well-tolerated dose. Importantly, the combination of CAt and 5-fluorouracil (5-FU) exhibited synergistic growth suppression and attenuated the development of 5-FU resistance. Overall, the findings suggest that CAt holds promise as a potential drug or adjuvant to improve melanoma treatment.