Featured Research

from universities, journals, and other organizations

Plant Compound Blocks Action Of Cancer Genes

Date:
August 31, 2000
Source:
Howard Hughes Medical Institute
Summary:
A plant compound that produces severe neural defects in developing embryos can block the action of mutated genes that produce basal cell skin carcinomas, the most common form of human cancer.

August 31, 2000 -— A plant compound that produces severe neural defects in developing embryos can block the action of mutated genes that produce basal cell skin carcinomas, the most common form of human cancer.

According to researchers at the Howard Hughes Medical Institute (HHMI) at The Johns Hopkins University School of Medicine, the studies in mouse cells suggest that the drug may be used to treat a number of cancers, including medulloblastomas in the brain and rhabdomyosarcomas in muscle. The finding also spotlights the promise of mechanism-based treatment approaches that target specific signaling pathways that are critical to a particular cancer. Conventional chemotherapy, in sharp contrast, kills cancer cells by attacking all proliferating cells—killing healthy tissue in the process.

In an article in the August 31, 2000, issue of the journal Nature, HHMI investigator Philip A. Beachy and his colleagues reported that the plant compound cyclopamine interferes with the action of the protein encoded by the gene, Smoothened. When Smoothened or its regulator Patched are mutated in skin cells, the cells grow without their normal constraints, and cancer can arise. Smoothened and Patched play a role in sensing the signal produced by Hedgehog, a critical protein in embryonic development.

Beachy's co-authors on the Nature article included Jussi Taipale and colleagues at Hopkins, and HHMI investigator Matthew P. Scott and his colleagues at Stanford University School of Medicine.

"It had long been known that animals that consumed plants containing cyclopamine suffered severe neural birth defects, including malformations that produced a single cyclopic eye," said Beachy. "And when we knocked out the mouse counterpart of the hedgehog gene, Sonic hedgehog, we saw an effect very much like that produced in animals by cyclopamine. So, that really rang a bell for us."

After initial experiments indicated that cyclopamine did not directly affect the Hedgehog protein, the scientists turned their attention to the two cellular targets that receive signals from Hedgehog—proteins produced by the genes Smoothened and Patched. While the Smoothened protein switches on cell division, the Patched protein acts as a cellular "brake," or tumor suppressor. Previous studies had shown that Hedgehog switches on cell division by binding to Patched, turning off its normal braking function, and allowing Smoothened to activate cell proliferation.

The scientists’ experiments ruled out that cyclopamine might thwart proliferation by activating the Patched protein. They found instead that when they deleted the Patched gene from mouse cells, cyclopamine could still turn off cell division. "Thus, we’d eliminated two red herrings—that cyclopamine affected either Hedgehog or Patched," said Beachy.

To test whether Smoothened was cyclopamine’s target, the scientists first produced mouse cells that expressed high levels of the Smoothened protein. Cyclopamine still suppressed activation of those cells. To investigate the limits of cyclopamine’s suppression, the scientists next tested the drug’s effects on mouse cells that possessed mutant activated forms of the Smoothened protein that were freed from control by Patched.

These mutant Smoothened-activated cells, the scientists found, proliferated regardless of cyclopamine treatment. Importantly, however, the mutant cells were suppressed by a more potent, synthetic form of cyclopamine.

"All these findings lead us to believe that Smoothened is the target of cyclopamine action, concluded Beachy. "And now that we have evidence that Smoothened is the target, we can further explore whether the interaction is direct or indirect."

Also, said Beachy, further experiments will test the effects of cyclopamine on tumors grown in mice that arise in cells lacking the Patched tumor suppressor.

Beachy emphasized that cyclopamine’s potential as a cancer therapy also illustrates the enormous potential of mechanism-based cancer therapies. "There are many efforts being made in universities and pharmaceutical companies to identify critical signaling pathways in tumors that could represent specific therapeutic targets," he said. "And these efforts will certainly lead to treatments far more effective and less toxic than standard chemotherapeutic agents, which are basically cell poisons."


Story Source:

The above story is based on materials provided by Howard Hughes Medical Institute. Note: Materials may be edited for content and length.


Cite This Page:

Howard Hughes Medical Institute. "Plant Compound Blocks Action Of Cancer Genes." ScienceDaily. ScienceDaily, 31 August 2000. <www.sciencedaily.com/releases/2000/08/000831074947.htm>.
Howard Hughes Medical Institute. (2000, August 31). Plant Compound Blocks Action Of Cancer Genes. ScienceDaily. Retrieved September 16, 2014 from www.sciencedaily.com/releases/2000/08/000831074947.htm
Howard Hughes Medical Institute. "Plant Compound Blocks Action Of Cancer Genes." ScienceDaily. www.sciencedaily.com/releases/2000/08/000831074947.htm (accessed September 16, 2014).

Share This



More Health & Medicine News

Tuesday, September 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Man Floats for 31 Hours in Gulf Waters

Man Floats for 31 Hours in Gulf Waters

AP (Sep. 16, 2014) A Texas man is lucky to be alive after he and three others floated for more than a day in the Gulf of Mexico when their boat sank during a fishing trip. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

AFP (Sep. 16, 2014) Since the arrival of Ebola in Ivory Coast, Ivorians have been abandoning their pets, particularly monkeys, in the fear that they may transmit the virus. Duration: 00:47 Video provided by AFP
Powered by NewsLook.com
Study Links Male-Pattern Baldness To Prostate Cancer

Study Links Male-Pattern Baldness To Prostate Cancer

Newsy (Sep. 16, 2014) New findings suggest men with a certain type of baldness at age 45 are 39 percent more likely to develop aggressive prostate cancer. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

      Technology News



      Save/Print:
      Share:

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins