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C Leuschner1 , W Hansel1 *
Pennington Biomed. Res. Center, Reprod. Biol., Baton Rouge, LA 1
A number of cancer cells including ovarian, breast, endometrial, testicular and prostate cancers, are known to express LH receptors. We have prepared a conjugate of a 23-amino acid lytic peptide (hecate) and a 15-amino acid segment of the -chain of LH. To test the concept that this conjugate selectively kills cells expressing the LH-receptor, it was added in varying concentrations (0-100 M) to the culture media of Chinese hamster ovary (CHO) cells (wild type) (no LH receptors), to transfected CHO cells expressing LH receptors and to transfected CHO cells pretreated with ZnCl2 to promote further expression of the LH receptors. Cell death at all concentrations was greater in ZnCl2 activated transfected CHO cells than in transfected (p<0.05), than in wild type cells (p<0.05). The conjugate showed concentration dependent toxicity in descending order for the following prostate cancer cell lines: BRF 41 T, a primary cell line (12.5 M), DU145, a brain metastatic cell (25 M), PC-3, a bone metastatic cell (50 M) and LNCaP a lymph node metastatic cell line (100 M). Removal of steroids from the culture medium decreased the sensitivity of all cell lines, except DU145, to the lytic conjugate (p<0.05). Additions of estradiol (E), DHT or FSH to the steroid free medium prior to treatment restored the sensitivity of BRF 41 T and LNCaP cells toward the conjugate; these treatments are all known to up-regulate LH receptors. The ability of E and DHT to restore sensitivity of these cell lines to the conjugate was abolished by the addition of the E antagonist tamoxifen. We conclude that the hecate/LH conjugate kills both androgen dependent and independent prostate cancer cells, and its toxicity appears to depend on the number of LH receptor sites present.
This abstract is being presented on Tuesday, August 3 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.