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:4/28/2016)... , ... April 28, 2016 , ... Head Over Heels ... 9 Western Championships. The competition will be held at the University of Montana on ... gymnasts west of the Mississippi River. , In order to qualify, Varize needed to ...
(Date:4/28/2016)... ... April 28, 2016 , ... ... open availability of a new CDISC standard, Clinical Trial Registry (CTR) XML. ... This innovative standard will make it possible to build applications that generate ...
(Date:4/28/2016)... ... April 28, 2016 , ... Cosmetic Town, an online ... cosmetictown.com . The forum section was recently revamped and upgraded to allow even more ... in use across the country. , According to the senior editor of Cosmetic Town, ...
(Date:4/28/2016)... ... 2016 , ... Greener Hydroponics is now offering a large selection of Smart ... organic farmers and nurseries according to Sales Manager Joe Steele who says, “Now is ... is to offer wholesale level pricing and ultra-fast shipping for growers of any size.” ...
(Date:4/28/2016)... ... April 28, 2016 , ... In 2011, TIME magazine ... the emerging field of biomechatronics, technology that marries human physiology with electromechanics. He continues ... He is also the Founder of BionX , a leader in the field ...
Breaking Medicine News(10 mins):
(Date:4/27/2016)... 27, 2016 ... in Zürich gab Strekin AG den Start ... zur Erhaltung des Resthörvermögens von Patienten, denen ... die umfassende Phase-II-Doppelblindstudie mit Placebo-Kontrollgruppe werden momentan ... wird während der Operation direkt ins Mittelohr ...
(Date:4/27/2016)... PARIS , April 27, 2016 ... Year-Over-Year Including 42% Growth in Recurring Consumable Sales  ... Mauna Kea Technologies (Euronext: MKEA, OTCQX: MKEAY) ... today announced its sales for the first quarter ended ... business and the execution of its commercial strategy. ...
(Date:4/27/2016)... 2016 Transparency Market Research has ... - Global Industry Analysis, Size, Share, Growth, Trends, and ... global skincare devices market was valued at US$ 7,255.8 ... a CAGR of 10.1% from 2015 to 2023 to ... the full Skincare Devices Market (Treatment Device - LED Therapy ...
Breaking Medicine Technology: