Characterization of the Contribution of Ceramide to Chemotherapy Sensitization in Breast Cancer Cells
Abstract
Our previous studies showed that PSC 833, the multidrug resistance modulator, increases cellular ceramide levels. Our studies in the first grant year demonstrated that PSC 833 increases ceramide levels via serine palmitoyl- transferase (SPT) activation. However, the effects of PSC 833 on other de novo enzymes, the scope of PSC 833/ceramide response in human breast cancer cells, and the extent to which other anticancer drugs impact SPT remain unknown. To this end, during the past year I have mastered several research techniques, analyzed experimental results, and prepared a manuscript for publication. We have demonstrated that PSC 833 activates SPT independently of SPT gene transcription, MAP kinase, and PKC. The effect of PSC 833 on SPT activation is closely related to its molecular structure. The research has also shown that PSC 833 induces ceramide generation in a broad spectrum of human breast cancer cell lines. Furthermore, we have demonstrated that SPT is the target enzyme in ceramide generation that is induced by other well known chemotherapeutic drugs, including etoposide, taxol, and retinoids. This is a significant finding which provides a novel approach to breast cancer treatment opening the door for new drug design targeting ceramide metabolism.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADA398144
Entities
People
- Hongtao Wang
- Myles C. Cabot