Navigation Links
Statin plus cancer drug deliver combo punch to brain cancer cells

Building on newly discovered genetic threads in the rich tapestry of biochemical signals that cause cancer, a Johns Hopkins Kimmel Cancer Center team has dramatically killed brain cancer cells by blocking those signals with a statin and an experimental antitumor drug.

The unlikely pairing of cholesterol-lowering lovastatin and cyclopamine killed 63 percent of medulloblastoma cells grown in the laboratory. By contrast, using either agent alone wiped out fewer than 20 percent of cells. The Hopkins researchers published their findings in the January issue of the American Journal of Pathology.

The researchers caution that the cyclopamine-lovastatin combination has yet to be tested in animals, much less people, but they conclude that the tumor cell-killing by the combo is tantalizing. Cyclopamine works by blocking the so-called "hedgehog" pathway, long known to promote and guide cell and organ growth. Excessive growth is the chief characteristic of cancer. The investigators believe that blocking hedgehog with cyclopamine makes cancer cells more susceptible to lovastatin.

Along with its cholesterol-clogging effects, lovastatin, sold under the trade name Mevacor, is known to curb destruction of proteins that put the brakes on cell growth, causing cancer cells to self-destruct through a process called apoptosis. The effects of the statin already is being studied in people at high risk for the deadly skin cancer, melanoma.

First extracted from corn lilies in the 1950s, cyclopamine is a powerful toxin known to stunt fetal development and cause birth defects in humans and animals. Its connection to anti-cancer efforts grew out of later insights into its blockage of hedgehog, which gets its name from spiky hairs that develop on fruit flies lacking the signal.

"We already knew from earlier research that hedgehog controls brain cell survival and growth, and that blocking signals in this pathway may stop uncontrolled growth of canc er cells," says Charles Eberhart, M.D., Ph.D., associate professor of pathology, ophthalmology and oncology. "But the new work shows the hedgehog blockade may halt another powerful cell-survival signal, and lovastatin could provide the added boost necessary to kill more cancer cells."

Specifically, Eberhart found links between the expression of key hedgehog-related genes in medulloblastoma cells and another cell signal already tied to cancer, Bcl-2. Eberhart and his team believed that combination of a hedgehog blockade and a pro-apoptosis drug like lovastatin would kill more cancer cells.

"Our experiments suggest that hedgehog's action is woven together with Bcl-2, best known for its role in causing B-cell lymphomas," he says. "Cancer cells thwart suicide by overproducing Bcl-2, assuring them a long life."

When the Hopkins researchers noticed that Bcl-2 and hedgehog expression increased in tandem in medulloblastoma cells, they tried adding hedgehog-blocking cyclopamine to the cells and found that Bcl-2 production dwindled and tumor cells died off.

Lead author and pathology fellow Eli E. Bar, Ph.D., said he was "surprised by the degree to which the drug combination was so effective."

According to Eberhart, only half of children with medulloblastoma survive. "And those that do survive can suffer debilitating side effects caused by current toxic therapies."


'"/>

Source:Johns Hopkins Medical Institutions


Related biology news :

1. Statins have neutral effect on risk of cancer
2. Statins stop hepatitis C virus from replicating
3. Statin treatment improves spatial memory in mouse models of Alzheimers
4. Viral DNA sequence a possible trigger for breast cancer
5. Enzyme, lost in most mammals, is shown to protect against UV-induced skin cancer
6. Its not all genetic: Common epigenetic problem doubles cancer risk in mice
7. Columbia research lifts major hurdle to gene therapy for cancer
8. Combination therapy boosts effectiveness of telomere-directed cancer cell death
9. Mitochondrial DNA mutations play significant role in prostate cancer
10. New imaging method gives early indication if brain cancer therapy is effective, U-M study shows
11. BRCA1 causes ovarian cancer through indirect, biochemical route
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/5/2017)... , April 5, 2017  The Allen Institute ... Allen Cell Explorer: a one-of-a-kind portal and dynamic digital ... 3D imaging data, the first application of deep learning ... human stem cell lines and a growing suite of ... platform for these and future publicly available resources created ...
(Date:4/3/2017)... April 3, 2017  Data captured by ... platform, detected a statistically significant association between ... to treatment and objective response of cancer ... to predict whether cancer patients will respond ... as well as to improve both pre-infusion potency ...
(Date:3/29/2017)... -- higi, the health IT company that operates the largest ... , today announced a Series B investment from BlueCross ... new investment and acquisition accelerates higi,s strategy to create ... health activities through the collection and workflow integration of ... and secures data today on behalf of over 36 ...
Breaking Biology News(10 mins):
(Date:10/12/2017)... ... October 12, 2017 , ... BioMedGPS ... the addition of its newest module, US Hemostats & Sealants. , SmartTRAK’s US ... absorbable hemostats, fibrin sealants, synthetic sealants and biologic sealants used in surgical applications. ...
(Date:10/11/2017)... ... October 11, 2017 , ... The ... context, enabling overexpression experiments and avoiding the use of exogenous expression plasmids. The ... transformative for performing systematic gain-of-function studies. , This complement to loss-of-function studies, ...
(Date:10/11/2017)... 11, 2017  VMS BioMarketing, a leading provider of patient ... Clinical Nurse Educator (CNE) network, which will launch this week. ... among health care professionals to enhance the patient care experience ... and other health care professionals to help women who have ... ...
(Date:10/11/2017)... ... October 11, 2017 , ... ... granted orphan drug designation to SBT-100, its novel anti-STAT3 (Signal Transducer and Activator ... osteosarcoma. SBT-100 is able to cross the cell membrane and bind intracellular STAT3 ...
Breaking Biology Technology: