Melanoma metastasis: What role does melanin play? (Review).

Melanoma is an extremely aggressive form of skin cancer that can spread to the lungs, brain, and liver, among other vital organs. Melanoma cells, unlike any other cancer cells, can produce significant amounts of melanin by a process known as melanogenesis, causing them to become heavily pigmented. Melanogenesis, specifically the melanin pigment, is well known for its ability to protect the skin from the harmful effects of UV light, which can lead to the development of skin cancer. Nevertheless, uncontrolled melanogenesis plays a role in the advancement of melanotic melanoma, and melanin pigments can reduce the effectiveness of radiotherapy and immunotherapy. Therefore, studies are being performed that focus on inhibiting melanogenesis to prevent melanoma metastasis. However, it is worth noting that, in addition to its UV­protective function, melanin also plays a role in preventing melanoma metastasis. Microphthalmia­associated transcription factor (MITF) and melanin have been demonstrated to attenuate the aggressiveness of melanoma by suppressing numerous essential metastatic processes. Eumelanin and pheomelanin (two types of melanin), which cause oxidative stress, can also prevent melanoma progression in the early stages. Hence, it is vital to explore the role of inducing melanogenesis rather than inhibiting melanogenesis in preventing melanoma metastasis.

Andrographolide and its analogues: versatile bioactive molecules for combating inflammation and cancer.

1. Andrographis paniculata (Burm. f) Nees, commonly known as 'king of bitters', is a herbaceous plant belonging to the Family Acanthaceae. It has been widely used for centuries in Asian countries like China, India, Thailand and Malaysia for the treatment of sore throat, flu and upper respiratory tract infections. 2. Andrographolide, 14-deoxy-11,12-didehydroandrographolide and neoandrographolide are examples of the major labdane diterpenoids isolated from A. paniculata. These bioactive molecules have exhibited varying degrees of anti-inflammatory and anticancer activities in both in vitro and in vivo experimental models of inflammation and cancer. 3. Extensive libraries of andrographolide analogues have been synthesised mainly by modifying the α,ß-unsaturated γ-butyrolactone moiety, the two double bonds Δ(8,(17)) and Δ(12,(13)) and the three hydroxyls at C-3 (secondary), C-14 (allylic) and C-19 (primary). Many of these synthetic analogues exhibit superior anticancer activity over the naturally occurring andrographolides. 4. Andrographolide and its derivatives have been shown to have anti-inflammatory effects in experimental models of asthma, stroke and arthritis, as well as in patients with upper respiratory tract infections. Andrographolide reduces the production of cytokines, chemokines, adhesion molecules, nitric oxide and lipid mediators, probably via inhibition of the nuclear factor (NF)-κB signalling pathway. 5. The anticancer mechanisms for andrographolide include inhibition of Janus tyrosine kinases-signal transducers and activators of transcription, phosphatidylinositol 3-kinase and NF-κB signalling pathways, suppression of heat shock protein 90, cyclins and cyclin-dependent kinases, metalloproteinases and growth factors, and the induction of tumour suppressor proteins p53 and p21, leading to inhibition of cancer cell proliferation, survival, metastasis and angiogenesis. 6. Andrographolide drug discovery is a promising strategy for the development of a novel class of anti-inflammatory and anticancer drugs.