A conjugate of doxorubicin and an analog of Luteinizing Hormone-Releasing Hormone shows increased efficacy against oral and laryngeal cancers

Krebs, Linda J.; Wang, Xiaopeng; Nagy, Atilla; Schally, Andrew V.; Prasad, Paras N.; Liebow, Charles

Next »Oral Oncology
Volume 38, Issue 7 , Pages 657-663, October 2002

A conjugate of doxorubicin and an analog of Luteinizing Hormone-Releasing Hormone shows increased efficacy against oral and laryngeal cancers

Linda J. Krebs
- Department of Physiology and Biophysics, and Department of Oral Biology, State University of New York at Buffalo, Buffalo, NY 14214, USA
- Institute for Lasers, Photonics and Biophotonics, Department of Chemistry, State University of New York at Buffalo, Buffalo, NY 14260, USA
- Corresponding author. Present address: University of Connecticut Health Center, Center for Molecular Medicine, 263 Farmington Avenue, MC 3101, Farmington, CT 06030, USA. Tel.: +1-860-679-2668; fax: +1-860-679-1920
Xiaopeng Wang
- Institute for Lasers, Photonics and Biophotonics, Department of Chemistry, State University of New York at Buffalo, Buffalo, NY 14260, USA
Atilla Nagy
- Veterans Affairs Medical Center and Tulane University School of Medicine, New Orleans, LA 70112, USA
Andrew V. Schally
- Veterans Affairs Medical Center and Tulane University School of Medicine, New Orleans, LA 70112, USA
Paras N. Prasad
- Institute for Lasers, Photonics and Biophotonics, Department of Chemistry, State University of New York at Buffalo, Buffalo, NY 14260, USA
Charles Liebow
- Department of Physiology and Biophysics, and Department of Oral Biology, State University of New York at Buffalo, Buffalo, NY 14214, USA
- Institute for Lasers, Photonics and Biophotonics, Department of Chemistry, State University of New York at Buffalo, Buffalo, NY 14260, USA

Received 21 November 2001; accepted 28 November 2001.

Abstract

A doxorubicin and [D-Lys⁶]Luteinizing Hormone-Releasing Hormone (LH-RH) conjugate, AN-152, was designed to target LH-RH receptor positive cells. AN-152 is more potent against a specific group of cancers than doxorubicin and has less peripheral toxicity. This therapy is potentially efficacious against many other types of malignancies. Here, AN-152 was tested on oral (KB) and laryngeal (HEp-2) carcinoma cells. LH-RH receptor presence was demonstrated by displacement binding assays. Cells were treated with 10 nM EGF or left untreated, then exposed to 0–10 μM AN-152. Cytotoxicity was assessed by MTT assay to determine ED₅₀ values. AN-152 association with the cells was monitored using two-photon laser scanning microscopy. AN-152 was more potent than doxorubicin in both KB and HEp-2 cell lines (P⩽0.05). Up-regulation of LH-RH receptors by epidermal growth factor (EGF) increased the entry and potency of AN-152 in KB cells, but not in HEp-2 cells. This novel approach may be effective against a variety of cancers.

Keywords: Targeted chemotherapy, LH-RH receptors, EGF, Oral and laryngeal cancer