Thermally targeted p21 peptide enhances bortezomib cytotoxicity in androgen-independent prostate cancer cell lines

Abstract

Prostate cancer remains one of the most common malignancies in men. Besides surgical resection, treatments for prostate cancer include hormone therapy, chemotherapy, and radiation therapy. Advancement of prostate cancer to an androgen-independent state limits the potential of conventional therapeutic approaches. Bortezomib, an FDA-approved proteosomal inhibitor for the treatment of myeloid leukemia, has been shown to have a positive effect on the inhibition of prostate cancer growth. Unfortunately, bortezomib has a very narrow therapeutic window, which can lead to severe side effects. Elastin-like polypeptide (ELP) is a genetically engineered, thermally responsive macromolecular carrier that enables a targeted delivery of the bound molecule because of its soluble property under normal physiologic conditions. In addition, ELP aggregates in response to mild hyperthermia. Using ELP as a carrier, it is possible to improve the pharmacological properties of the therapeutic drug as well as reduce toxicity in normal tissues. In this work, we have investigated the combination treatment of androgen-independent prostate cancer cells with bortezomib and the C-terminal part of the p21(WAF1/CIP1) protein bound to the ELP carrier. We have found that combination treatment with bortezomib and ELP-bound p21(WAF1/CIP1) protein leads to increased cell cycle arrest as well as apoptosis with respect to single treatments. We believe that this approach represents a promising direction for the treatment of androgen-independent prostate cancer.