Navigation Links
Drug slows prostate tumor growth by keeping vitamin A active
Date:11/6/2007

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
staci.goldberg@aacr.org
267-646-0616
American Association for Cancer Research
Source:Eurekalert

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:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... Southern ... and Jennifer Huggins, PharmD ’17, along with clinical associate professor Janice Frueh, ... cardiovascular diseases during the 15th Annual Women’s Health Conference. The SIU School ...
(Date:10/13/2017)... ... , ... Ellevate Network, the leading network for professional women, brought together some ... at their inaugural Summit in New York City in June. The event was livestreamed ... over 3 million. To watch the Mobilize Women video, click here . ...
(Date:10/13/2017)... , ... October 13, 2017 , ... “The Journey: From ... every danger possible to save lost souls in the Philippines. “The Journey: From the ... is a dedicated teacher of the Bible. She has taught all ages and currently ...
(Date:10/12/2017)... ... 2017 , ... The company has developed a suite of ... authorities worldwide. From Children’s to Adults 50+, every formula has been developed by ... , These products are also: Gluten Free, Non-GMO, Vegan, Soy Free, Non-Dairy*, Preservative ...
(Date:10/12/2017)... ... 2017 , ... Dr. Parsa Mohebi, the Los Angeles based ... the newly revamped Cosmetic Town journal section, featuring articles written by ... as Follicular Unit Extraction (FUE). , Dr. Mohebi says “I enjoy ...
Breaking Medicine News(10 mins):
(Date:10/11/2017)... 11, 2017  Hill-Rom Holdings, Inc. ("Hill-Rom") (NYSE: HRC), ... in Las Piedras, Puerto Rico , ... Following a ... sustained minor structural damage, temporary loss of power and ... been completed, manufacturing operations have resumed, and the company ...
(Date:10/7/2017)... , Oct. 6, 2017   Provista, a ... than $100 billion in purchasing power, today announced a ... information. The Newsroom is the online home ... trends, infographics, expert bios, news releases, slideshows and events. ... to a wealth of resources at their fingertips, viewers ...
(Date:10/4/2017)... to the Centers for Disease Control and Prevention (CDC), influenza vaccination ... is helping communities across Massachusetts , Connecticut ... flu shots through the end of the month. *Some exclusions ... ... shot is by the end of October, according to the Centers for ...
Breaking Medicine Technology: