Oxidative stress and antioxidants in the pathophysiology of malignant melanoma

Obrador, Elena; Liu‐Smith, Feng; Dellinger, Ryan W.; Salvador, Rosario; Meyskens, Frank L.; Estrela, José M.

doi:10.1515/hsz-2018-0327

Cited by 88 publications

(92 citation statements)

References 225 publications

(235 reference statements)

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“…Melanoma cells exhibited significantly higher oxidative stress and produced larger amounts of ROS when compared to melanocytes and surrounding normal tissue [107]. ROS stimulated melanoma progression and metastatization through a number of changes, including (i) DNA modification, (ii) cell proliferation, (iii) tissue remodeling, (iv) immune surveillance escape, (v) pro-metastatic processes activation [108,109]. Malorni and colleagues demonstrated that males express lower levels of anti-oxidants, such as glutathione (GSH), catalase and superoxide dismutase (SOD) when compared to females, thus exhibiting a higher rate of oxidative stress [110,111].…”

Section: Sex and Immunitymentioning

confidence: 99%

Sex and Gender Disparities in Melanoma

Bellenghi

Puglisi

Pontecorvi

et al. 2020

Cancers

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Worldwide, the total incidence of cutaneous melanoma is higher in men than in women, with some differences related to ethnicity and age and, above all, sex and gender. Differences exist in respect to the anatomic localization of melanoma, in that it is more frequent on the trunk in men and on the lower limbs in women. A debated issue is if—and to what extent—melanoma development can be attributed to gender-specific behaviors or to biologically intrinsic differences. In the search for factors responsible for the divergences, a pivotal role of sex hormones has been observed, although conflicting results indicate the involvement of other mechanisms. The presence on the X chromosome of numerous miRNAs and coding genes playing immunological roles represents another important factor, whose relevance can be even increased by the incomplete X chromosome random inactivation. Considering the known advantages of the female immune system, a different cancer immune surveillance efficacy was suggested to explain some sex disparities. Indeed, the complexity of this picture emerged when the recently developed immunotherapies unexpectedly showed better improvements in men than in women. Altogether, these data support the necessity of further studies, which consider enrolling a balanced number of men and women in clinical trials to better understand the differences and obtain actual gender-equitable healthcare.

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Section: Sex and Immunitymentioning

confidence: 99%

Sex and Gender Disparities in Melanoma

Bellenghi

Puglisi

Pontecorvi

et al. 2020

Cancers

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“…Oxidative stress has been considered as a major contributor to the development of skin cancers, such as melanoma [144][145][146]. Accordingly, antioxidants, including resveratrol, have been used to prevent and treat skin cancer [147][148][149], although exacerbation and increased risk of cancers have been reported [150,151].…”

Section: Anticancermentioning

confidence: 99%

Role of Resveratrol in Regulating Cutaneous Functions

Wen

Zhang

Yang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Protective role of the skin is against external insults and maintenance of electrolyte homeostasis of the body. Cutaneous dysfunction can account for the development of both cutaneous and systemic disorders. Thus, improvements in cutaneous functions can benefit a number of extracutaneous and cutaneous functions. Resveratrol, a natural ingredient, displays multiple benefits for various systems/organs, including the skin. The benefits of resveratrol for cutaneous functions include stimulation of keratinocyte differentiation and antimicrobial peptide expression, inhibition of keratinocyte proliferation and cutaneous inflammation, UV protection, anticancer, antiaging, and inhibition of melanogenesis. The mechanisms of action of resveratrol include activation of sirtuin 1 and nuclear factor erythroid 2-related factor 2, and inhibition of mitogen-activated protein kinase signaling. Evidence suggests that topical resveratrol could be a valuable alternative not only for daily skin care, but also for the prevention and treatment of various cutaneous disorders. This review summarizes the benefits of resveratrol for cutaneous functions.

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“…Oxidative stress and intracellular redox state balance are essential. Evidence also shows that high intracellular ROS levels could cause an increase in antioxidant enzymes for compensation and homeostasis balance [7,[21][22][23]. Based on our previous findings that antioxidants, such as SOD2 and peroxiredoxin-1 (PRDX1), are elevated in dabrafenib resistant (DR) melanoma cells identified from a proteomics screen [7], we aimed to assess SOD2 and PRDX1 levels in BRAF and MEK inhibitor-resistant cells.…”

Section: Sod2 and Nf-κb Levels Are Increased In Braf Pathway Inhibitomentioning

confidence: 99%

BRAF Mutant Melanoma Adjusts to BRAF/MEK Inhibitors via Dependence on Increased Antioxidant SOD2 and Increased Reactive Oxygen Species Levels

Yuan

Mishra

Patel

et al. 2020

Cancers

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B-Rapidly Accelerated Fibrosarcoma (BRAF) mutations are found in about 50% of melanoma patients. Treatment with Food and Drug Administration (FDA)-approved BRAF and MAP/ERK kinase (MEK) inhibitors has improved progression free and overall survival of patients with BRAF mutant melanoma. However, all responders develop resistance typically within 1 year of treatment with these inhibitors. Evidence indicates that reactive oxygen species (ROS) levels are elevated after BRAF pathway inhibition treatment. We aim to decipher the role of mitochondrial antioxidant proteins relative to ROS levels and BRAF pathway inhibitor resistance. We observed BRAF mutant melanoma cells treated with the combination of a MEK inhibitor (trametinib) and a BRAF inhibitor (dabrafenib), exhibited elevated ROS levels, both in in vitro and in vivo melanoma models. We next generated trametinib- and dabrafenib-resistant (TDR) cells and found increased ROS levels after acquisition of resistance. An immunofluorescence experiment showed an increase of DNA damage in TDR cell lines. Furthermore, we observed that TDR cells increased superoxide dismutase 2 (SOD2), an antioxidant, at both mRNA and protein levels, with the upregulation of the transcription factor Nuclear Factor (NF)-κB. Knockdown of SOD2 significantly reduced the growth of BRAF pathway inhibitor-resistant cells. In addition, the results indicate that TDR cells can be re-sensitized to BRAF pathway inhibitors by the ROS scavenger, N-Acetyl Cysteine (NAC). Overall, these data indicate that BRAF pathway inhibitor-resistant cells can compensate for elevated ROS via increased expression of the antioxidant SOD2.

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Oxidative stress and antioxidants in the pathophysiology of malignant melanoma

Abstract: Oxidative stress and antioxidants in the pathophysiology of malignant melanoma.

Cited by 88 publications

References 225 publications

Sex and Gender Disparities in Melanoma

Sex and Gender Disparities in Melanoma

Role of Resveratrol in Regulating Cutaneous Functions

BRAF Mutant Melanoma Adjusts to BRAF/MEK Inhibitors via Dependence on Increased Antioxidant SOD2 and Increased Reactive Oxygen Species Levels

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