Alternative Options for Skin Cancer Therapy via Regulation of AKT and Related Signaling Pathways

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.

UBIAD1 and CoQ10 protect melanoma cells from lipid peroxidation-mediated cell death

“…To further understand the effect of UBIAD1 KD in melanoma cells we examined a series of signaling pathways which play key roles in protein synthesis, survival, proliferation and metabolism ( Figs. S2A–F ) [ [32] , [33] , [34] , [35] ]. Compared to control cells, UBIAD1 KD affects phosphorylation of AKT(Ser473) protein, S6 signaling and AMPK in SkMel28, while UBIAD1 KD affect significantly only AKT and mTOR/s6 signaling in A375.…”

Identification of potential inhibitors of cutaneous Melanoma and Non-Melanoma skin cancer cells through in-vitro and in-silico screening of a small library of Phenolic compounds

“…[14][15][16][17] Although inhibitors of BRAF and MEK have shown significant survival benefits in clinical trials, the prognostic significance of BRAF and NRAS mutations outside of clinical trials remains unclear. [14][15][16][17] The overexpression and activation of V-akt murine thymoma viral oncogene homolog (AKT, also known as protein kinase B) 11 and related signaling pathways are also known to be major contributing factors in many cancers, including some lung cancers, esophageal squamous cell carcinomas and various skin cancers. 18 Other signaling pathways, including those involving mitogen-activated protein kinase (MAPK), [19][20][21] phosphoinositide 3-kinase (PI3K)-Akt, [22][23][24] mammalian target of rapamycin (mTOR), 22,25,26 nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB), 27 Janus kinase-signal transducer and activator of transcription (JAK-STAT), transforming growth factor β (TGF-β), 28,29 and Notch are shown to play an important role in skin homeostasis, and in melanoma and non-melanoma cancer progression.…”

“…[7][8][9] Arresting proliferation or inducing programmed cell death in proliferating cancer cells is another effective cancer therapy option. [10][11][12][13] Significant advances have been made toward a better understanding of mechanisms through which melanoma and non-melanoma skin cancers are triggered and sustained. Hotspot mutations of the oncogenes BRAF and NRAS are the most common genetic alterations in cutaneous melanoma, and such mutations are known drivers of all melanomas, as mutant BRAF and NRAS can independently activate the downstream MEK1/2-ERK1/2 oncogenic signal transduction pathway.…”

Phytochemical Profile and Anticancer Activity from Medicinal Plants Against Melanoma Skin Cancer: A Review

“…Skin cancer is one of the most common global public health problems, with increased mortality rates and morbidity and treatment costs annually (Thuncharoen et al, 2013;Yahya et al, 2019;Hwang et al, 2020). Despite the abundance of data on the presentation of skin cancer in white individuals, there is a paucity of data regarding disease morphology and risk factors in darker-skinned individuals because the incidence of skin cancer is relatively higher in white individuals (Gordon et al, 2022;Manci et al, 2022).…”