Genetic risk? Chondroitin sulphate supplements linked to skin cancer growth
The supplement, a structural component of cartilage, has been linked to benefits for joint health and is commonly used by people with arthritis - often in combination with glucosamine sulphate.
However, writing in Molecular Cell, researchers said the nutrient was found to boost growth in melanoma cells carrying the V600E mutation of the BRAF gene.
Chondroitin sulphate (CS) had no effect on other types of melanoma cells, the team noted - adding that the V600E mutation occurs in roughly half of melanomas.
Led by researchers from the Winship Cancer Institute at Emory University School of Medicine, USA, the team reported that mice implanted with V600E tumours, who were given CS at equivalent doses to those in human dietary supplements, displayed accelerated tumour progression. Mice also shown signs of resistance to the chemotherapy drug vemurafenib, which is used to treat V600E-positive melanoma patients.
There are two main form of CS which occur in human dietary supplements are chondroitin-4-sulphate (C4S) and chondroitin-6-sulphate (C6S). The C4S form was found to be cancer promoting.
“Our results reveal a pathologic link between dietary supplements and specific oncogenic mutations, such that C4S treatment results in increased circulating and consequently intracellular C4S levels that promote BRAF V600E tumour growth,” commented lead author Professor Jing Chen.
The scientists also found that the polymeric chain form, but not the enzymatically digested or single disaccharide unit forms of CS, increased melanoma proliferation. The researchers stated that further research was needed to explain this particular finding, which they found puzzling.
Enzyme driven proliferation
The scientists found that an enzyme, chondroitin sulfate glucuronyl transferase (CSG), drove the proliferation of B-raf melanomas through its role in helping the formation of polymeric CS.
Inhibition of CSG might be a therapeutic target in treatment of B-raf V600E melanomas, suggested the researchers. However, such inhibitors are not currently available and if developed, might raise the risk of of muscular skeletal problems, cautioned the researchers.
“Inhibition of the CSG –C4S axis at the whole organism level may cause health problems due to chondroitin sulphate deficiency, such as, but not limited to, osteoarthritis and joint pain,” they said.
Significance
Although confirmation is needed in human epidemiological studies, the findings are a warning regarding the use of CS supplements in people with BRAF V600E melanoma or pre-cancerous lesions.
"We want to be cautious about these results, and they should be followed up," said Chen. "There is not a lot of hard data on dietary supplement use. We found that we had to add a line to the forms melanoma patients fill out about their histories, since we weren't asking before."
Nevertheless, “Our findings have additional clinical impact, suggesting that taking chondroitin sulphate with C4S as a primary component as a dietary supplement for osteoarthritis or other health problems may not only worsen the disease burden in patients with BRAF V600E melanoma or other related cancers but also increase cancer risk in individuals with BRAF V600E-positive pre-malignant lesions.
“In addition, our data also demonstrate that treatment with C4S confers drug resistance to BRAF V600E-expressing melanoma cells in vitro and in vivo when treated with BRAF inhibitors. Taken together, these findings suggest that C4S as a dietary supplement may commonly increase cancer risk and/or confer drug resistance.
“Patients with BRAF V600E melanoma in particular should avoid using chondroitin sulphate as a dietary supplement,” concluded the researchers.
Source: Molecular Cell
Published online: 15 March 2018. DOI: 10.1016/j.molcel.2018.02.010
“Dietary supplement chondroitin-4-sulfate exhibits oncogene-specific pro-tumor effects on BRAF V600E melanoma cells”
Authors: Ruitling Lin, Jing Chen et al
