Parkinson's Disease Drug Carbidopa has Anticancer potential

Highlights:

• Carbidopa, a drug used to treat Parkinson’s disease (PD) has been found to have significant anticancer properties in this current study
• Many of the current chemotherapeutic agents are associated with severe unwanted and long lasting side effects
• Since Carbidopa is FDA approved, and found to be a safe drug, further studies to investigate its anticancer effect merit consideration

Anti-Parkinson’s disease drug Carbidopa found to have anti-cancer effects and could emerge as potential anticancer drug in the future, according to a recent study at the Texas Tech University Health Sciences Center in the USA. The findings of the study appear in the Biochemical Journal, and could probably explain why the incidence of several cancers, except melanoma is lower in persons with Parkinson’s disease.

"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 lead study author Dr Yangzom Bhutia from Texas Tech University Health Sciences Center in the USA.

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Carbidopa As Anticancer Agent - The Advantages

Carbidopa is an FDA approved drug to treat Parkinson’s disease. It has been proven to be safe and well tolerated. Thus it would be relatively easier to explore the role of this drug to treat cancer, while significantly reducing the time, effort and money that would otherwise be required to be spent in investigating a totally new drug.

Professor Aideen Sullivan from the University College Cork is a Parkinson's disease expert who was not involved in the research. When asked about the current study, she commented: "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."

Testing the Efficacy of Carbidopa as Anticancer Agent

In this study, Bhutia and her team, including collaborators from Japan and India, assessed the anticancer effects of carbidopa on a human pancreatic cancer cell line as well as in mouse models of pancreatic cancer.

• It was seen that carbidopa significantly reduced growth and multiplication of cancer cells both in the cell line as well as mice.

Although the team believes that carbidopa could have wide ranging anticancer effects, they chose to focus on pancreatic cancer because of the limited treatment options for this form of the disease and poor survival and long-term prognosis.

" Pancreatic cancer, especially the pancreatic ductal adenocarcinoma, is the most lethal of all cancers with a dismal survival rate," commented Bhutia. "Carbidopa as an anti-cancer agent to treat pancreatic cancer would be something truly amazing.”

"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."

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Safety Aspect of Carbidopa – Found to be Safe

The standard dose of carbidopa for Parkinson's disease patients is 200 mg/day, although, even a dose as high as 450 mg/day, has been found to be free of side effects. This study was not carried out in humans; nevertheless, the dose of carbidopa given to mice, which inhibited tumor growth was equivalent to a dose of less than 400 mg/day in humans, which is considered to be safe for patients.

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Mechanism of Action of Carbidopa

The aryl hydrocarbon receptor (AhR) protein plays a critical role in cancer and stimulation of this protein appears promising to treat several including breast, colon and pancreatic cancer. Bhutia and team demonstrated that carbidopa activates AhR and believe this may account, at least in part for its anticancer properties.

The author of an accompanying commentary to the research article Professor Stephen Safe, Texas A&M University, remarked: "This receptor was initially identified as the critical target that mediates the toxicity of "dioxin" and related compounds; however, results of this study with carbidopa and several other reports are demonstrating that the AhR is a therapeutic target not only for cancer but many other diseases."

About Carbidopa - In Brief

L-Dopa has been used to treat PD symptoms, but associated with several adverse effects including nausea. This is because only a very small amount of the drug (5-10%) enters the brain, while the rest of the drug is converted to dopamine in other parts of the body, resulting in undesirable side effects.

Carbidopa is given along with L-Dopa to prevent the peripheral conversion of L-Dopa to dopamine i.e. in tissues outside the brain. Fortunately, carbidopa does not enter the brain and therefore does not interfere with L-Dopa effect in the brain.

Parkinson's disease is a neurodegenerative disorder affecting movement and motor skills. Symptoms include shaking, stiffness and difficulty in walking. It occurs due to reduced dopamine production by neurons in the brain. Currently, there is no cure and treatments aim to reduce symptoms.

Future Plans

• The team plans to investigate the possibility of additional targets of carbidopa other than the aryl hydrocarbon receptor (AhR) protein to explain its anticancer effects
• Bhutia plans to work closely with oncologists to design and conduct clinical trials in cancer patients to confirm whether carbidopa would be useful as an anticancer drug in humans

In conclusion, if carbidopa is approved as an anticancer agent, it would be good news for cancer patients as well as treating physicians. However, it would be important to first establish the effectiveness of carbidopa in specific cancer types and conduct clinical trials.

References:

1. Parkinson's disease drug shows anticancer effects - (https://www.eurekalert.org/emb_releases/2017-09/bs-pdd092617.php)

Source-Medindia