Abstract
Global environmental pollution has led to human exposure to ultraviolet (UV) radiation due to the damaged ozone layer, thereby increasing the incidence and death rate of skin cancer including both melanoma and non-melanoma. Overexpression and activation of V-akt murine thymoma viral oncogene homolog (AKT, also known as protein kinase B) and related signaling pathways are major factors contributing to many cancers including lung cancer, esophageal squamous cell carcinoma and skin cancer. Although BRAF inhibitors are used to treat melanoma, further options are needed due to treatment resistance and poor efficacy. Depletion of AKT expression and activation, and related signaling cascades by its inhibitors, decreases the growth of skin cancer and metastasis. Here we have focused the effects of AKT and related signaling (PI3K/AKT/mTOR) pathways by regulators derived from plants and suggest the need for efficient treatment in skin cancer therapy.
Highlights
Skin cancer is one of the most frequent cancers worldwide [1,2], with increasing annual costs and morbidity [3,4]
Polyphyllin I-induced apoptosis and autophagy was mediated via the downregulation of pPI3K, pAKT and pmTOR expression
Herbacetin showed anticarcinogenic and anticancer activities in A431 cutaneous squamous cell carcinoma and SK-MEL-5 melanoma in vitro at 10 and 20 μM concentrations, and in a mouse model of two-stages skin carcinogenesis induced by 7,12-dimethylbenz[α]-anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) and solar UV (48 kJ/m2 UVA, 2.9 kJ/m2 UVB) as well as in a SK-MEL-5 cell xenograft mouse model in vivo following topical treatment (100 and 500 nmol) and i.p. injection (0.2 and 1 mg/kg) [38]
Summary
Skin cancer is one of the most frequent cancers worldwide [1,2], with increasing annual costs and morbidity [3,4]. NMSC includes basal cell carcinoma (~80%) and squamous cell carcinoma (~16%) and melanoma accounts for ~4% of all skin cancer [5]. An estimated 7,700,000 new cases of NMSC, including 5,900,000 basal cell carcinomas and 1,800,000 squamous cell carcinomas, have been reported globally including 195 countries accounting for 65,000 cancer deaths [2,7]. The major environmental risk factors for skin cancer (melanoma and NMSC) include UVA, UVB and UVC [6,8]. Vemurafenib is a competitive inhibitor of BRAF kinase activity, and especially inhibits melanoma with a V600 mutation Treatment with these therapeutic agents is associated with severe side effects and a low quality of life including nausea, hair loss and increased risk of infection. Natural compounds are the preferred choice due to their reduced risk of toxicity and cost-effectiveness
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