A study of the differentiation and dedifferentiation of three human melanoma cell lines

Pigment formation in melanocytes is the end-point of a series of biochemical reactions involving numerous melanocyte-specific proteins including, inter alia, the enzymes tyrosinase, tyrosinase-related protein-1 (TRP-1 ), tyrosinase-related protein-2 (TRP-2) and the melanosomal protein encoded by the P gene. The function of tyrosinase and TRP-2 have recently been clarified, but the roles of TRP-1 and the P protein remain unknown. The first aim of this study was to examine the expression of these proteins at a transcriptional and translational level in order to provide more insight into possible mechanisms which may lead to changes in melanoma cell differentiation. Three human melanoma cell lines (Mel 1, Mel-2 and Mel-3) with varying levels of pigmentation (highly melanised to amelanotic) were examined by enzyme assays and RNA quantification methods. The results showed gene expression of all four genes in the highly melanised Mel-1 and amelanotic Mel-3 cell lines. TRP-1 and TRP-2 were not expressed in the melanised Mel-2 cell line. These results suggest that there is no correlation between tyrosinase gene expression and level of pigmentation in these cell lines. In addition, they show that the level of pigmentation of human melanoma cell does not necessarily correlate to the level or pattern expression of the tyrosinase gene family. Furthermore the results of the present study show that the P gene is expressed at high levels in all the melanoma cell lines, irrespective of their level of pigmentation . The second broad aim of this study was to determine the effect of melanocytestimulating hormone (a melanogenic stimulator) on melanogenesis in Mel-1 cells. Mel-1 cells, which were exposed to 10⁻⁷ M MSH for 6 days, showed no change in tyrosinase mRNA levels, but the mRNA levels of TRP-1, TRP-2 and the P gene were reduced. This suggested the presence of a possible co-ordinated down-regulatory mechanism in the Mel-1 cells under the influence of MSH

Mitochondrial targeting of wild-type and mutant human protoporphyrinogen oxidase (PPOX)

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Rooibos (Aspalathus linearis) and its Major Flavonoids — Potential Against Oxidative Stress-Induced Conditions

Reactive species are products of normal cellular metabolism and may be deleterious or beneficial. At low/moderate concentrations, reactive species are involved in physiological roles including cell signalling, defense against infectious agents and mitogenic responses. However, unbalanced defense mechanism of antioxidants, overproduction of reactive species or incorporation of free radicals into the living system from the environment may result in oxidative stress, a deleterious process that can lead to damage of important cell structures, including lipids and membranes, proteins and nucleic acids. The role of oxidative stress as a contributing factor in the pathophysiology of various diseases is increasingly being recognized, and augmenting the oxidative defense capacity of the cell through the intake of antioxidants as a way of preventing free radical-mediated cellular injuries is becoming a popular strategy. Much attention is being focused on the health beneficial role of phenolic phytochemicals derived from plants. They are considered to play an important role as physiologically functional foods and for the prevention of clinical conditions related to oxidative stress, even though their modes of action may still not be fully understood. Rooibos (Aspalathus linearis) is a popular South African tisane enjoyed for its taste and aroma. Rooibos has been made in the Cederberg mountain region of South Africa for generations and has been used medicinally for alleviation of allergies, asthma, infantile colic and skin problems. The potential antioxidative, immune-modulating, chemopreventive and chemotherapeutic actions of rooibos have been reported in several studies. This review provides a comprehensive data on the current knowledge of the biological and chemotherapeutic activity of rooibos and its major flavonoids. Most recent in vitro and in vivo (animal and human) studies were conducted with special attention paid to clinical conditions in which oxidative stress has been implicated. The conclusion described directions for future rooibos research to establish its activity and utility as a human chemopreventive and therapeutic agent

St John's Wort (Hypericum perforatum L.) photomedicine: hypericin-photodynamic therapy induces metastatic melanoma cell death

Hypericin, an extract from St John's Wort ( Hypericum perforatum L. ), is a promising photosensitizer in the context of clinical photodynamic therapy due to its excellent photosensitizing properties and tumoritropic characteristics. Hypericin-PDT induced cytotoxicity elicits tumor cell death by various mechanisms including apoptosis, necrosis and autophagy-related cell death. However, limited reports on the efficacy of this photomedicine for the treatment of melanoma have been published. Melanoma is a highly aggressive tumor due to its metastasizing potential and resistance to conventional cancer therapies. The aim of this study was to investigate the response mechanisms of melanoma cells to hypericin-PDT in an in vitro tissue culture model. Hypericin was taken up by all melanoma cells and partially co-localized to the endoplasmic reticulum, mitochondria, lysosomes and melanosomes, but not the nucleus. Light activation of hypericin induced a rapid, extensive modification of the tubular mitochondrial network into a beaded appearance, loss of structural details of the endoplasmic reticulum and concomitant loss of hypericin co-localization. Surprisingly the opposite was found for lysosomal-related organelles, suggesting that the melanoma cells may be using these intracellular organelles for hypericin-PDT resistance. In line with this speculation we found an increase in cellular granularity, suggesting an increase in pigmentation levels in response to hypericin-PDT. Pigmentation in melanoma is related to a melanocyte-specific organelle, the melanosome, which has recently been implicated in drug trapping, chemotherapy and hypericin-PDT resistance. However, hypericin-PDT was effective in killing both unpigmented (A375 and 501mel) and pigmented (UCT Mel-1) melanoma cells by specific mechanisms involving the externalization of phosphatidylserines, cell shrinkage and loss of cell membrane integrity. In addition, this treatment resulted in extrinsic (A375) and intrinsic (UCT Mel-1) caspase-dependent apoptotic modes of cell death, as well as a caspase-independent apoptotic mode that did not involve apoptosis-inducing factor (501 mel). Further research is needed to shed more light on these mechanisms

The impact of solar ultraviolet radiation on human health in sub-Saharan Africa

Photoprotection messages and ‘SunSmart’ programmes exist mainly to prevent skin cancers and, more recently, to encourage adequate personal sun exposure to elicit a vitamin D response for healthy bone and immune systems. Several developed countries maintain intensive research networks and monitor solar UV radiation to support awareness campaigns and intervention development. The situation is different in sub-Saharan Africa. Adequate empirical evidence of the impact of solar UV radiation on human health, even for melanomas and cataracts, is lacking, and is overshadowed by other factors such as communicable diseases, especially HIV, AIDS and tuberculosis. In addition, the established photoprotection messages used in developed countries have been adopted and implemented in a limited number of sub-Saharan countries but with minimal understanding of local conditions and behaviours. In this review, we consider the current evidence for sun-related effects on human health in sub-Saharan Africa, summarise published research and identify key issues. Data on the prevalence of human diseases affected by solar UV radiation in all subpopulations are not generally available, financial support is insufficient and the infrastructure to address these and other related topics is inadequate. Despite these limitations, considerable progress may be made regarding the management of solar UV radiation related health outcomes in sub-Saharan Africa, provided researchers collaborate and resources are allocated appropriately

The anti-proliferative and anti-bacterial activity of argan oil and crude saponin extract from Argania spinosa (L.) skeels

INTRODUCTION: Argan oil is a well-known cosmeceutical that is commercially available. It is traditionally used for the treatment of acne and skin inflammation among others. The objective of this study was to assess the anti-proliferative and antibacterial activities of argan oil and a crude saponin extract from the argan tree (Argania spinosa (L.) Skeels) that is endemic to Morocco. MATERIALS AND METHODS: The anti-proliferative activity of argan oil and the crude saponin extract was assessed by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay on A431; HaCat; HeLa; MCF-7 and UCT-Mel 1 cells. The antibacterial activity was evaluated by the broth microdilution method against two species of bacteria: Cutibacterium acnes and Prevotella intermedia. RESULTS: The results of this study indicated that the argan oil sample did not inhibit the cell growth of the specified cell lines up to 1000µg/ml, while the crude saponin extract had low anti-proliferative activity. The minimal inhibitory concentration (MIC) values for both the argan oil and the crude saponin extract were found to be 500µg/ml against Cutibacterium acnes. No antibacterial activity from the argan oil or the crude saponin extract was evident against Prevotella intermedia up to a concentration of 12.5mg/ml. CONCLUSION: The results of this study indicated that argan oil and the crude saponin extract might have direct inhibitory effects on the growth and proliferation of Cutibacterium acnes. This finding supports the use argan oil as a treatment for acne vulgaris.National Research Foundationhttp://www.phcogfirst.com/content/pharmacognosy-journalpm2020Plant Production and Soil Scienc

Philosophy of education in a new key: Cultivating a living philosophy of education to overcome coloniality and violence in African Universities

In this conversational article, we consider cultivating decoloniality in university education by drawing upon Jacques Ranci ere’s (2010) notion of a living philosophy. Ranci ere’s (2010) living philosophy holds the possibility of both a medium and a space for a re-thinking and a re-contemplation of what life is in relation to what it might be. Through engaging and sharing real human experiences from and within African societies and universities, we (re)imagine decoloniality as a fiction brought to life through a living philosophy of education. In this regard, we proffer eight points of departure and reflection

The phenomenon of skin lightening: Is it right to be light?

AbstractChemicals capable of lightening the skin – variously known as skin-bleaching, skin-lightening, depigmenting, skin-evening and skin-brightening agents – are among the most commonly used skin preparations in the world. Globally, Africa reportedly exhibits a high prevalence of skin lightener use. In this review, we provide both clinical and social perspectives on skin lightener use in Africa, with particular emphasis on South Africa. We narratively explore the timeline associated with skin lightener use in South Africa and attempt to interweave the social rhetoric of this specific paradigm. Despite the risks associated with exposing the skin to known constituents of these formulations, such as hydroquinone and mercury, chronic use continues. In spite of legislation banning hydroquinone and mercury in cosmetics in South Africa, these ingredients are present in widely available products. We recommend better implementation of policies and greater ethical responsibility of multinational cosmetic companies in addition to the initiation of a system of random product testing and penalties that could improve industry compliance