The goal of this proposal is to determine if malignant brain tumors are sensitive to the Chinese herbal remedy Zen Sheng Ping (ZSP, also known as antitumor B). ZSP is a combination of six herbs which has been shown to prevent the progression of pre-neoplastic lesions of the esophagus. It also appears to slow or prevent progression of lung cancer in both humans and in animal models. It was recently found that ZSP downregulates the Notch signaling pathway in lung cancer. The Notch pathway plays a critical role in the proliferation of lung tumor cells, suggesting Notch inhibition is an important mechanism by which the anti-tumor effects of ZSP are mediated. This raises the possibility that ZSP might also successfully treat other Notch- dependant tumors. We have shown that Notch signaling plays a critical role in the growth of several types of brain cancer, including the most common malignant brain tumors in children (medulloblastoma) and adults (glioblastoma). Other Notch-dependent neoplasms that might be treated using ZSP include pancreatic, breast and ovarian carcinomas, as well as melanoma. Small-molecule Notch inhibitors appear block the formation and growth of brain tumor xenografts by depleting stem-like cancer cells, but this class of compounds has been associated with significant toxicity. We therefore plan to investigate whether ZSP might represent a more potent and/or less toxic treatment for malignant brain tumors by blocking Notch activity. Project Narrative: The goal of this proposal is to determine if malignant brain tumors can is treated using a Chinese herbal remedy known as Zen Sheng Ping (ZSP). It was recently found that ZSP inhibits an important molecular pathway known as Notch in cancer cells. We have shown that Notch signaling plays a critical role in the growth of several types of brain cancer, including the most common malignant brain tumors in children (medulloblastoma) and adults (glioblastoma) ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AT003893-01A1
Application #
7383042
Study Section
Special Emphasis Panel (ZAT1-DB (27))
Program Officer
Sorkin, Barbara C
Project Start
2008-05-01
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
1
Fiscal Year
2008
Total Cost
$246,000
Indirect Cost
Name
Johns Hopkins University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Lim, Kah Jing; Rajan, Kda; Eberhart, Charles G (2012) Effects of Zeng Sheng Ping/ACAPHA on malignant brain tumor growth and Notch signaling. Anticancer Res 32:2689-96
Lim, Kah Jing; Bisht, Savita; Bar, Eli E et al. (2011) A polymeric nanoparticle formulation of curcumin inhibits growth, clonogenicity and stem-like fraction in malignant brain tumors. Cancer Biol Ther 11:464-73