Abstract 5518: Bladder tumor-targeting peptide-mediated anti-tumor activity of a pro-apoptotic peptide

• Published in: Cancer research (Chicago, Ill.) Ill.), 2010-04, Vol.70 (8_Supplement), p.5518-5518
• Main Authors: Jung, Hyun-Kyung, Kwak, Mi-Kyung, Lee, Eun-Ju, Son, Ji Woong, Park, Rang-Woon, Kim, In-San, Lee, Byung-Heon
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM10-5518

Bladder carcinoma is the most common urothelial malignancy in developed countries and the rate of recurrence is pretty high. Using phage display, we have previously identified a bladder tumor-targeting peptide with the amino acid sequence of CSNRDARRC (namely, Bld-1). Bld-1 was shown to target bladder tumor in carcinogen-induced tumor-bearing rats. A synthetic pro-apoptotic peptide KLAKLAKKLAKLAK, called (KLAKLAK)2, has been demonstrated to induce apoptotic cell death of tumor cells. In this study, we used Bld-1 as a homing domain to help the pro-apoptotic peptide selectively bind to bladder tumor cells and allow its internalization. Bld-1 preferentially bound to HT-1376 bladder tumor cells, while little binding to A549 lung tumor cells was observed. Confocal microscopic analysis demonstrated that Bld-1 was efficiently internalized into HT-1376 cells. Bld-1-conjugated D-enantiomer D(KLAKLAK)2 was synthesized and incubated with HT-1376 cells for 24, 48, and 72 h. Bld-1-D(KLAKLAK)2 exerted its cytotoxic activity on HT-1376 cells in a dose- and time-dependent manner. In addition, D(KLAKLAK)2 alone also showed cytotoxic activity after 48 h treatment but this was in a lesser extent as compared to Bld-1-D(KLAKLAK)2. The cell death induced by Bld-1-D(KLAKLAK)2 was due to apoptosis as shown by annexin V and propidium iodide staining. Bld-1-D(KLAKLAK)2 more efficiently inhibited tumor growth in HT-1376 bladder tumor-bearing mice than D(KLAKLAK)2. These results suggest that Bld-1-D(KLAKLAK)2 might be a useful therapeutic agent for targeted therapy of bladder tumor. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5518.