Navigation Links
Agent orange chemical, dioxin, attacks the mitochondria to cause cancer, says Penn research team
Date:12/17/2007

PHILADELPHIA Researchers with the University of Pennsylvania School of Veterinary Medicine have demonstrated the process by which the cancer-causing chemical dioxin attacks the cellular machinery, disrupts normal cellular function and ultimately promotes tumor progression.

The team identified for the first time that mitochondria, the cellular sub-units that convert oxygen and nutrients into cellular fuel, are the target of tetrachlorodibenzodioxin, or TCDD. The study showed that TCDD induces mitochondria-to-nucleus stress signaling, which in turn induces the expression of cell nucleus genes associated with tumor promotion and metastasis.

The mechanism the research team has described is directly relevant to understanding incidences of breast and other cancers in human populations exposed to these chemicals. With a better understanding of this underlying cellular mechanism, researchers hope to improve their understanding of tumor growth and promotion.

"Now that we have identified this signaling mechanism we can look at ways to disrupt this complex chain of events, said Narayah Avadhani, chair of the Department of Animal Biology at Penns School of Veterinary Medicine and the studys lead investigator. Our ultimate goal is to block the propagation of this mitochondrial stress signaling and inhibit the expression of the proteins that combine to assist cancer growth.

A well-characterized mechanism of TCDD action occurs through activation of arylhydrocarbon receptors, AhR, by directly binding to the protein subunits. Activated AhR mediates the transcriptional activation of many genes including those involved in fatty acid metabolism, cell cycle regulation and immune response. The present study, however, shows that TCDD starts the chain of events that promote tumor progression in vivo by directly targeting mitochondrial transcription and induction of mitochondrial stress signaling. A unique feature of this TCDD-induced signaling is that it does not involve the action of AhR but occurs through increased calcium levels in cells and activation of calcium responsive factors. A net result of signaling cascade is slowing down of cellular apoptosis, increased cell proliferation and tumor cell metastasis. Taken together, this study describes a novel mechanism of TCDD-induced tumor progression and emergence of metastatic cancer cells.

TCDD is the most toxic compound in the dioxin family. Formed as a by-product during waste incineration, paper, chemical and pesticide manufacturing, it was the toxic ingredient in Agent Orange and closed the Love Canal in Niagara Falls. The public health impact of dioxin, according to the Environmental Protection Agency, compares to that of the pesticide DDT.


'/>"/>

Contact: Jordan Reese
jreese@upenn.edu
215-573-6604
University of Pennsylvania
Source:Eurekalert

Related medicine news :

1. Is 4 agents decoction (Si Wu Tang) efficacious in treating primary dysmenorrhea?
2. Investigational Agent Targeting Metabotropic Glutamate 2/3 Receptors Demonstrates Antipsychotic Activity in Humans, Study in Nature Medicine Finds
3. Replidyne Pipeline Featured at 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy
4. MassMutual Agent Honored by Insurance Industry for Extraordinary Service to Client
5. Sagent Pharmaceuticals Inc. Completes $53 Million Series A Financing
6. ABR-Affinity BioReagents Expands 100% Quality Guarantee
7. Inside job: new radioactive agents for colon cancer work inside cells
8. ABR -- Affinity BioReagents Announces Launch of New Website
9. The Bank of New York Mellon Recognized as Change Agent Shaping the Direction of Healthcare Transaction Processing
10. EpiCept to Present Preclinical Studies of EPC2407 in Combination With Anti-Angiogenic and Chemotherpeutic Agents at the AACR-NCI-EORTC International Conference
11. Imagentix Offers Extension of Warrants
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/28/2016)... of America (PRWEB) , ... May 28, 2016 , ... ... SuperCloset knows all too well the day to day issues, struggles and obstacles veterans’ ... The Helping Veterans Grow Project provides active or retired military veteran(s) with a ...
(Date:5/28/2016)... (PRWEB) , ... May 28, 2016 , ... After a year and a half of ... was an extraordinary event. The Multiple Pathways of Recovery Conference was held May 2 ... the country and the United Kingdom came together to explore the many pathways individuals use ...
(Date:5/27/2016)... ... ... Southland Log Homes , designer and manufacturer of America’s Favorite Log Home™, ... found on its website at SouthlandLogHomes.com. , The designs of the wood barn ... of timber post and beam construction. The result is a barn that not ...
(Date:5/27/2016)... ... May 27, 2016 , ... An influential resource amongst nurses and professionals ... shed lights on the variety of topics detailing why we appreciate nurses in so ... this career has gone from being in a major recession to one of the ...
(Date:5/27/2016)... ... May 27, 2016 , ... An ... bolstered by inspiring human-interest stories, courtesy of awareness-driven celebrities and thought leaders. It ... leading advocates, associations and industry leaders such as Bioness. , As patients ...
Breaking Medicine News(10 mins):
(Date:5/25/2016)... 2016 According to market research ... and Demand Forecast to 2022 - Industry Insights by ... published by P&S Market Research, the global insulin delivery ... and it is expected to grow at a CAGR ... pump segment is expected to witness the fastest growth ...
(Date:5/25/2016)... NORTH CHESTERFIELD, Va. , May 25, 2016 ... commercially-available next-generation sequencing test for wounds and infections. ... fungi, ALL parasites, and select viruses. The test ... infected area. David G. ... advanced molecular testing to facilitate wound healing: "We ...
(Date:5/25/2016)... MedDay, a biotechnology company focused on the treatment ... "High doses of biotin in progressive multiple sclerosis: extension phase ... Ayman Tourbah , Principal Investigator of the Phase 3 ... Neurology (EAN) in Copenhagen, Denmark . The ... on Sunday, 29 May 2016 from 14:45 to 16:15 CEST ...
Breaking Medicine Technology: