Carbidopa, a medicine approved for the treatment of Parkinson’s disease, also has shown anti-cancer effects in lab-grown human cells and mice, according to the results of a new study. The findings help explain why cancer incidence usually is lower in Parkinson’s patients — with the exception of skin cancer — and suggest that carbidopa may be explored further as an anticancer drug.
The study, “Carbidopa is an activator of aryl hydrocarbon receptor with potential for cancer therapy,” was published in the Biochemical Journal.
“Carbidopa is an FDA-approved drug for treating Parkinson’s disease. Hence, clinical trials can be conducted right away to evaluate its efficacy in humans as an anticancer drug,” explained study lead author, Yangzom Bhutia, PhD, from Texas Tech University Health Sciences Center.
Parkinson’s disease patients are treated with a combo of carbidopa and levopoda for halting disease symptoms. While studies had shown that levodopa had no anti-cancer properties, less was known about the effects of carbidopa on cancer cells.
“Interestingly, no one has previously suspected carbidopa as a potential player in this phenomenon,” said Bhutia. “Carbidopa is never used by itself as a drug for any disease. But our data show that carbidopa by itself possesses the anticancer effect. We believe that the reduced incidence of most cancers in Parkinson’s disease patients is due to carbidopa.”
“We also postulate that the increased incidence of melanoma in Parkinson’s disease patients is most likely due to [levodopa], and not due to carbidopa, because [levodopa] is the precursor for melanin synthesis, a metabolic pathway that occurs exclusively in melanocytes,” added Bhutia.
Her team, together with collaborators from Japan and India, decided to test the potential anti-cancer effects of carbidopa in a human pancreatic cancer cell line, as well as in mouse models of pancreatic cancer, a disease marked by high mortality rates and very few therapeutic options.
Administration of carbidopa significantly inhibited cancer cell growth both in culture and in mice.
“Pancreatic cancer, especially the pancreatic ductal adenocarcinoma, is the most lethal of all cancers with a dismal survival rate,” said Bhutia. “Carbidopa as an anti-cancer agent to treat pancreatic cancer would be something truly amazing. Given the fact that it is an FDA-approved drug, re-purposing the same drug for cancer treatment would be tremendously cost- and time-saving,” she said.
Carbidopa is recommended for adult Parkinson’s patients in a 200 mg/day dose, but researchers have shown that the dose can be increased to up to 450 mg/day without causing side effects. Mice received an equivalent dose of less than 400 mg/day in humans, within the safety range, and at this concentration the drug exerted antitumor effects.
Previous studies had shown that activation of a particular protein – the aryl hydrocarbon receptor (AhR) – is a potential therapeutic strategy for several cancers, including pancreatic cancer. Researchers identified that carbidopa activates AhR-mediated signalling, suggesting it may exert its anti-cancer properties via this pathway.
“Our laboratory is actively working to determine if there are additional targets for this drug related to its potency as an anticancer drug,” Bhutia added. “We would like to partner with oncologists to design and conduct clinical trials in cancer patients to establish whether or not carbidopa would be useful as an anticancer drug in humans.”
“With increasing interest in the re-purposing of drugs, to reduce costs and time needed to get a drug to market, it is timely for investigators to explore the potential anticancer properties of anti-Parkinson’s therapies,” Parkinson’s disease expert, professor Aideen Sullivan from the University College Cork, Ireland commented on the findings. “Since carbidopa has already been proven to be safe and well-tolerated by people with Parkinson’s, its application in cancer treatment, where most current therapies are associated with severe and long-lasting side-effects, will be welcomed by patients.”
“Nevertheless, due to the complexity of cancer cell biology, it will be important to firstly conduct studies on the effectiveness of carbidopa in specific types of cancer,” he concluded.