Joint supplement speeds melanoma cell growth

March 15, 2018

Chondroitin sulfate, a dietary supplement taken to strengthen joints, can speed the growth of a type of melanoma, according to experiments conducted in cell culture and mouse models.

The results are scheduled for publication in Molecular Cell.

One particular mutation in the B-raf gene (V600E) can be found in about half of melanomas. Jing Chen, PhD and colleagues found that chondroitin sulfate can boost growth by melanoma cells carrying the V600E mutation, but not other melanoma cells. Chondroitin sulfate, given to mice with implanted V600E tumors, has a similar effect at levels comparable to those seen in humans when it is used as a dietary supplement. V600E tumors in mice fed with chondroitin sulfate also showed resistance to vemurafenib, a small molecule B-raf inhibitor currently used to treat V600E-positive melanoma patients.

While unconfirmed in human epidemiological studies, the findings are a warning to oncologists, and people at an elevated risk of melanoma, regarding potential risks of dietary supplements. Chondroitin sulfate, a structural component of cartilage, is often recommended for the treatment of osteoarthritis, in combination with other compounds such as glucosamine.

It is possible that someone with precancerous lesions containing the V600E mutation, who takes chondroitin sulfate, might accelerate the growth of those cells, or that V600E positive cancer patients taking chondroitin sulfate might have a higher risk of relapse, says Chen, professor of hematology and medical oncology at Winship Cancer Institute of Emory University.

"We want to be cautious about these results, and they should be followed up," he says. "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."

He adds that a large study from the state of Washington showed no link between chondroitin sulfate and prostate or lung cancer risk, although genetic background was not examined.

Working with Chen, instructor Ruiting Lin, PhD discovered the effect while evaluating various metabolic enzymes for whether they would be necessary to drive proliferation in mutated B-raf melanoma. Lin observed that the enzyme chondroitin sulfate glucuronyltransferase (CSGlcA-T, or CSG here for short) emerged in her screen. CSG is important for forming the chondroitin sulfate polymer.

Chen says he and Lin were surprised to see CSG in their screen, saying: "We had to dig back in the literature to confirm that chondroitin sulfate does get taken up by cells." The finding that chondroitin sulfate can drive melanoma cell growth suggests a signaling role inside cells, which scientists are unfamiliar with. The researchers saw that only the polymeric form of chondroitin sulfate (not the digested form) would influence B-raf melanomas, which they call puzzling in the paper.

While their current paper also identifies CSG as an anticancer drug target, compounds that inhibit the enzyme are not readily available. Inhibitors would need to be tested for potential side effects such as joint pain or the deterioration of connective tissue.

It is possible that CSG may combine with other oncogenes besides B-raf V600E, Chen says. His lab previously showed that a high-fat, low-carbohydrate "ketogenic" diet can also accelerate the growth of V600E melanoma cells.
Winship co-authors include Michael Rossi, PhD, Ragini Kudchadkar, MD, David Lawson, MD and Sagar Lonial, MD.

The research was supported by the National Cancer Institute (CA140515, CA183594, CA174786), Joel A. Katz Music Medicine Fund and the T.J. Martell Foundation. Lin is a fellow of the Leukemia & Lymphoma Society, and Chen is a Winship Cancer Institute 5K Scholar.

Emory Health Sciences

Related Melanoma Articles from Brightsurf:

Boosting treatments for metastatic melanoma
University of Cincinnati clinician-scientist Soma Sengupta, MD, PhD, says that new findings from her and Daniel Pomeranz Krummel's, PhD, team might have identified a treatment-boosting drug to enhance effectiveness of therapies for metastatic cancer and make them less toxic, giving patients a fighting chance at survival and improved quality of life.

A promising new tool in the fight against melanoma
An Edith Cowan University (ECU) study has revealed that a key blood marker of cancer could be used to select the most effective treatment for melanoma.

New targets for melanoma treatment
A collaborative study led by Monash University's Biomedicine Discovery Institute and the Olivia Newton-John Cancer Research Institute (ONJCRI) has uncovered new markers (HLA-associated peptides) that are uniquely present on melanoma tumours and could pave the way for therapeutic vaccines to be developed in the fight against melanoma.

Innovative smartphone-camera adaptation images melanoma and non-melanoma
An article published in the Journal of Biomedical Optics (JBO), ''Point-of-care, multispectral, smartphone-based dermascopes for dermal lesion screening and erythema monitoring,'' shows that standard smartphone technology can be adapted to image skin lesions, providing a low-cost, accessible medical diagnostic tool for skin cancer.

Antihistamines may help patients with malignant melanoma
Can a very common allergy medicine improve survival among patients suffering from the serious skin cancer, malignant melanoma?

Blood test for deadly eye melanoma
A simple blood test could soon become the latest monitoring tool for the early detection of melanoma in the eye.

Analysis of melanoma in US by age groups
This study used registry data to determine annual rates of melanoma in pediatric, adolescent, young adult and adult age groups, and the findings suggest an apparent decrease among adolescent and young adults between 2006 and 2015 but increases in older adults.

Vitamin D dials down the aggression in melanoma cells
Vitamin D influences the behaviour of melanoma cells in the lab by making them less aggressive, Cancer Research UK scientists have found.

B cells linked to immunotherapy for melanoma
Immunotherapy uses our body's own immune system to fight cancer.

Five things to know about melanoma
'Five things to know about ... melanoma' in CMAJ (Canadian Medical Association Journal) provides a brief overview of this malignant skin cancer for physicians and patients.

Read More: Melanoma News and Melanoma Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to