Featured Research

from universities, journals, and other organizations

Compounds show promise in blocking STAT3 signaling as treatment for osteosarcoma

Date:
April 11, 2011
Source:
Nationwide Children's Hospital
Summary:
Researchers have discovered that two new small molecule inhibitors are showing promise in blocking STAT3, a protein linked to the most common malignant bone tumor, osteosarcoma. These small molecule inhibitors -- one derived from a portion of the turmeric spice -- may serve as a new, non-toxic treatment for these deadly tumors.

A study appearing in the journal Investigational New Drugs and conducted by researchers at Nationwide Children's Hospital, discovered that two new small molecule inhibitors are showing promise in blocking STAT3, a protein linked to the most common malignant bone tumor, osteosarcoma. These small molecule inhibitors -- one derived from a portion of the turmeric spice -- may serve as a new, non-toxic treatment for these deadly tumors.

Osteosarcoma is aggressive and its treatment outlook has not changed significantly over the last 20 years. Treatment consists of a combination of toxic chemotherapy and aggressive surgical resection. Yet, despite these options, patients have at most a 50-to-60 percent five-year disease-free survival rate.

"The outcome for patients with advanced or metastatic osteosarcoma continues to be dismal, emphasizing the need for new therapies," said the study's lead author Jaiyuh Lin, PhD, principal investigator in the Center for Childhood Cancer in The Research Institute at Nationwide Children's Hospital. "Directly targeting STAT3 signaling represents a potential therapeutic approach to treating this type of cancer."

STAT3 is a member of a protein family that plays a role in relaying signals from cytokines and growth factors. The abnormal activation of STAT proteins is becoming more commonly associated with unrestricted cell growth and transformation of normal cells into malignant cells. Abnormal STAT3 activation has been seen in human and canine osteosarcoma cell lines and shows cancer-causing-capabilities in cultured cells and mouse models.

"Recent experiments aimed at blocking STAT3 signaling have been successful, resulting in the inhibition of growth and the induction of death in tumors," said Dr. Lin, also a faculty member at The Ohio State University College of Medicine. "They have also shown that blocking STAT3 in normal cells is neither harmful nor toxic."

Dr. Lin and his team evaluated two newly developed compounds, LLL12 and FLLL32, to determine their ability to inhibit STAT3 activity in human osteosarcoma cells. FLLL32 is derived from the dietary agent curcumin, the principal compound in the popular Indian spice turmeric.

Findings showed that both agents were able to inhibit STAT3 activity and suppressed tumor growth in the mouse model that was developed using human osteosarcoma cells, and primary osteosarcoma xenograft provided by Nationwide Children's Hospital scientist, Peter Houghton, PhD, directly from a patient.

"This study suggests that LLL12 and FLLL32 should be suitable for targeting osteosarcoma and possibly certain types of cancer cells with persistently activated STAT3," said Dr. Lin. "This approach deserves further exploration as a potential treatment of osteosarcoma."

The development of both STAT3 inhibitors is in the collaboration with Drs. Chenglong Li, Pui-Kai Li and Jim Fuchs from The Ohio State University College of Pharmacy.


Story Source:

The above story is based on materials provided by Nationwide Children's Hospital. Note: Materials may be edited for content and length.


Journal Reference:

  1. Grace-Ifeyinwa Onimoe, Aiguo Liu, Li Lin, Chang-Ching Wei, Eric B. Schwartz, Deepak Bhasin, Chenglong Li, James R. Fuchs, Pui-kai Li, Peter Houghton, Amanda Termuhlen, Thomas Gross, Jiayuh Lin. Small molecules, LLL12 and FLLL32, inhibit STAT3 and exhibit potent growth suppressive activity in osteosarcoma cells and tumor growth in mice. Investigational New Drugs, 2011; DOI: 10.1007/s10637-011-9645-1

Cite This Page:

Nationwide Children's Hospital. "Compounds show promise in blocking STAT3 signaling as treatment for osteosarcoma." ScienceDaily. ScienceDaily, 11 April 2011. <www.sciencedaily.com/releases/2011/04/110411152637.htm>.
Nationwide Children's Hospital. (2011, April 11). Compounds show promise in blocking STAT3 signaling as treatment for osteosarcoma. ScienceDaily. Retrieved July 29, 2014 from www.sciencedaily.com/releases/2011/04/110411152637.htm
Nationwide Children's Hospital. "Compounds show promise in blocking STAT3 signaling as treatment for osteosarcoma." ScienceDaily. www.sciencedaily.com/releases/2011/04/110411152637.htm (accessed July 29, 2014).

Share This




More Health & Medicine News

Tuesday, July 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Generics Eat Into Pfizer's Sales

Generics Eat Into Pfizer's Sales

Reuters - Business Video Online (July 29, 2014) Pfizer, the world's largest drug maker, cut full-year revenue forecasts because generics could cut into sales of its anti-arthritis drug, Celebrex. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Nigeria Ups Ebola Stakes on 1st Death

Nigeria Ups Ebola Stakes on 1st Death

Reuters - Business Video Online (July 29, 2014) Nigerian authorities have shut and quarantined a Lagos hospital where a Liberian man died of the Ebola virus, the first recorded case of the highly-infectious disease in Africa's most populous economy. David Pollard reports Video provided by Reuters
Powered by NewsLook.com
Running 5 Minutes A Day Might Add Years To Your Life

Running 5 Minutes A Day Might Add Years To Your Life

Newsy (July 29, 2014) According to a new study, just five minutes of running or jogging a day could add years to your life. Video provided by Newsy
Powered by NewsLook.com
Ebola Outbreak Poses Little Threat To U.S.: CDC

Ebola Outbreak Poses Little Threat To U.S.: CDC

Newsy (July 29, 2014) The Ebola outbreak in West Africa poses little threat to Americans, according to officials with the Centers for Disease Control and Prevention. 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