Applicability of Plant Extracts in Preclinical Studies of Melanoma: A Systematic Review

Abstract

Melanoma is the most aggressive form of skin cancer and arises from melanocyte gene mutation. This disease is multifactorial, but its main cause is the excessive exposure to ultraviolet radiation. Currently, available chemotherapy has shown little expressive results, which may justify the high use of natural products to treat this cancer. We performed a systematic review to compile the results of studies carried out in murine models and investigated the effect of plant extracts on melanoma treatment. Papers were selected in MEDLINE/Pubmed and Scopus according to the PRISM statement. Search filters were developed using three parameters: plant extract, melanoma, and animal model. The 35 identified studies were all submitted to the criteria described in the ARRIVE guidelines. The different extracts showed antiangiogenic, antimetastatic, antioxidant, and anti-inflammatory activity, and also proved to be effective in cell cycle modulation and apoptosis evasion. Bias analysis evidenced the absence of standardized experimental designs, as well as failures in statistical tests and in the presentation of results. The analysis of the studies suggests that the use of plant extracts is effective for the treatment of melanoma in murine models.

Figure 1

Flow diagram of the systematic review literature search results. Based on [16].

Figure 2

Summary of the studies describing the plant species, families, used parts of plants, toxicity tests, and popular indications.

Figure 3

Article results. NF-κB (nuclear factor kappa B), AP-1 (activator protein 1), AKT (protein kinase B), PI3K (phosphatidylinositol-3-kinase), PCNA (proliferating cell nuclear antigen), MMP-2 and MMP-9 (metalloproteinases 2 and 9), PKCα (protein kinase C alpha), TIMP-1 and TIMP-2 (metallopeptidase inhibitors 1 and 2), NO (nitric oxide), GGT (gama-glutamil transpeptidase), KDR/FIK-1 (kinase insert domain receptor/fetal liver kinase 1), NK (natural killers), IL (interleukin), IFN-γ (interferon gama), TNF-α (tumor necrosis factor alfa), GM-CSF (granulocit-monocit colony stimulating factor), VEGF (vascular endothelial growth factor), FGF (fibroblast growth factor), EGF (epidermal growth factor), TGF-β (transforming growth factor-beta), HIF-1α (hypoxia-inducible factor-1α), COX-2 (cyclooxygenase 2), GSH (glutathione), and iNOS (inducible nitric oxide synthase).