A Novel Class of Galectin-1 Inhibitors for Prostate Cancer Therapy
Abstract
In Year 3 of this award, we investigated whether S-LLS133 is more effective in expressing nuclear or cytosolic, and whether treatment of S-LLS133 induces nuclear localization of Gal-1. Both C4-2B cells that express low levels of Gal-1 and 22Rv1 cells that express high levels of Gal-1 demonstrated enhanced expression of Gal-1 upon treatment with S-LLS133. Moreover, Gal-1 localized to the nucleus upon treatment with S-LLS133 for 72 hours at 1 micrometer. To evaluate the effects of S-LLS133 on the response to cabazitaxel, we tested both cabazitaxel and S-LLS133 in organoids derived from abiraterone-resistant prostate cancer PDX tumors expressing different levels of galectin 1. S-LLS133 sensitized cabazitaxel-resistant tumors to this chemotherapeutic agent. We performed PK study on S-LLS133 and discovered that the compound is rather stable in vivo. We performed a Maximum Tolerated Dose (MTD) experiment to identify the highest dose of S-LLS133 that can be safely administered to mice. No signs of toxicity were observed in mice that received S-LLS133 at 10-50mg/kg for 5 consecutive days. Taken together, this suggests that S-LLS133 may be a good drug to target gal-1 sensitive castration resistant prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1191235
Entities
People
- Huanyao Gao
- Liewei Wang
- Malvina Tsamouri
- Paramita M Ghosh
- Rebecca B. Armenta
- Ruiwu Liu
- Tsung-chieh Shih
Organizations
- University of California