Navigation Links
Drug slows prostate tumor growth by keeping vitamin A active

SINGAPORE -- A novel compound that blocks the breakdown of retinoic acid, derived from vitamin A, is a surprisingly effective and promiscuous agent in treating animal models of human prostate cancer, say investigators from the University of Maryland, Baltimore (UMB).

Daily injections of the agent VN/14-1 resulted in up to a 50 percent decrease in tumor volume in mice implanted with human prostate cancer cells, reported Aakanksha Khandelwal, Ph.D., today at the American Association for Cancer Research Centennial Conference on Translational Cancer Medicine. No further tumor growth was seen during the five-week study, Khandelwal reports.

Importantly, VN/14-1 exerted its effects in multiple ways, which is the hallmark of a so-called promiscuous drug, according to the studys senior investigator, Vincent C.O. Njar, Ph.D., associate professor in the Department of Pharmacology and Experimental Therapeutics within UMBs School of Medicine.

This potent agent causes cancer cells to differentiate, forcing them to turn back to a non-cancerous state − which is what we expected it would do − but it also stops cancer growth by arresting the cell cycle and pushes cells to die by inducing programmed cell death, Njar said.

These functions were unexpected and wonderfully surprising, he said. I am not aware that any other drug currently used to treat prostate cancer targets so many pathways.

Vitamin A, when converted by the body into retinoic acid, is known to be involved in maintaining the normal growth of cells, and other research has shown that prostate cancer cells contain five to eight times less retinoic acid than normal prostate cells. Njars laboratory developed a number of compounds, including VN/14-1, with the aim of inhibiting the normal breakdown of retinoic acid in cancer cells.

The agent is similar in function to the well-known acne and anti-aging therapy, Retin-A, as well as to the leukemia drug Vesanoid. These products, known as retinoids, add all-trans retinoic acid (ATRA) to skin or cancer cells. VN/14-1, which is a retinoic acid metabolism blocking agent (RAMBA), works by inhibiting the breakdown of ATRA, keeping more retinoic acid available within cancer cells so that the chemical can redirect these cells back into their normal growth patterns, which includes programmed cell death.

Our idea is that rather than give extra ATRA, we would prevent ATRA already available within cells from being broken down, Njar said. We now call VN/14-1 an atypical RAMBA because in addition to blocking ATRA metabolism, it has other multiple desirable anti-cancer effects.

VN/14-1 works by blocking the CYP26 enzyme that actually transforms ATRA into inactive compounds, he says. The researchers have successfully tested VN/14-1 in breast cancer cells and have been funded to study the compound in preclinical studies that can lead to a Phase I human clinical trial.

In this study, the researchers found in mouse models of human prostate cancer that a 5 mg/kg (milligram per kilogram) dose injected daily resulted in a 33 percent reduction in tumor size; a dose twice as large reduced tumors by 50 percent.

They also tested a dose of 20 mg/kg through oral and intravenous administration to study the concentration of VN/14-1 in the blood over time in rats. They found that the amount of VN/14-1 in the blood after oral administration was exceptionally high compared to intravenous VN/14-1. This indicates that VN/14-1 should be tested orally as this is the preferred route of drug administration in humans, Njar says. Giving an agent orally in small doses is exactly what you want in an anti-cancer drug, he said.

Contact: Staci Vernick Goldberg
American Association for Cancer Research

Related medicine news :

1. Health Insurance Premium Growth Slows for Fourth Straight Year
2. Philanthropic Giving for Health Care Slows in 2006 in both U.S. and Canada, According to Association for Healthcare Philanthropys Annual Report on Giving
3. Conventional prognostic factors fail to explain better prostate cancer survival in most Asian men
4. First biomarker discovered that predicts prostate cancer outcome
5. Frequent Prostate Screens Fail to Improve Aggressive Cancer Diagnoses
6. New male sling procedure helps prostate cancer survivors who suffer from urinary incontinence
7. Us TOO Launches National SEA Blue Campaign for Prostate Cancer Awareness Month
8. Red wine compound shown to prevent prostate cancer
9. Barbershop Talks Cut Black Mens Prostate Cancer Risk
10. Generic prostate drug helps find high-risk cancers early
11. Finasteride unlikely to induce high grade prostate cancers
Post Your Comments:
(Date:11/25/2015)... ... November 25, 2015 , ... SCOTTSDALE, AZ) - ... surgeon specializing in both surgical and non-surgical treatments, announced the expansion of his ... Facial Plastic Surgery. , Highly trained and nationally recognized for his natural ...
(Date:11/25/2015)... D.C. (PRWEB) , ... November 25, 2015 , ... Today, ... fatalities on our nation’s roadways has dropped below 10,000 for the first time since ... 10,076 in 2013. , According to data released by the National Highway Traffic Safety ...
(Date:11/25/2015)... ... November 25, 2015 , ... An unlikely combination of ... a way for homeless people to have a more dignified and comfortable night’s ... whereby they are repurposing plastic bags into sleeping mats for the homeless. ...
(Date:11/25/2015)... ... November 25, 2015 , ... Bunion ... in an early celebration of the early holiday shopping season. Starting Wednesday November ... (normally $33.95 ea). Black Friday promotional pricing is in addition to any automatic ...
(Date:11/24/2015)... ... 2015 , ... Young patients with a wide variety of dental needs can ... S. Lele, who are pediatric dentists in Tucson, AZ . Unlike traditional treatment ... system causes minimal discomfort and bleeding to the patient during treatment and the following ...
Breaking Medicine News(10 mins):
(Date:11/24/2015)... 25, 2015 WuXi PharmaTech (Cayman) Inc. ("WuXi" ... open-access R&D capability and technology platform company serving the ... China and the ... extraordinary general meeting of shareholders held today, the Company,s ... and approve the previously announced agreement and plan of ...
(Date:11/24/2015)... 2015  Array BioPharma Inc. (Nasdaq: ARRY ... Ron Squarer , will present at the ... The public is welcome to participate in the ... website.Event:Piper Jaffray Annual Healthcare ConferencePresenter:  , Ron Squarer, ... p.m. Eastern Time Webcast: , ...
(Date:11/24/2015)... , Nueva York , ... Biomedical Devices (ABD), fabricante del Avery Breathing Pacemaker ... Anders Jonzon , MD; Ph.D. como consultor clínico. ...   --> Foto - ... --> El doctor Jonzon es un fisiólogo ...
Breaking Medicine Technology: