Induction of programmed cell death in Kaposi's sarcoma cells by preparations of human chorionic gonadotropin

Background: Isolation of the first neoplastic acquired immunodeficiency syn drome-related Kaposi's sarcoma (KS) cell line (KS Y-1) has furthered unders tanding of the pathogenesis of KS. Studies with KS Y-1 cells have indicated that inhibition of KS cell proliferation occurs in early pregnancy in mice and after treatment with certain commercial preparations of human chorioni c gonadotropin (hCG, a pregnancy hormone purified from urine), The activity of the commercial preparations has been attributed to an hCG-associated fa ctor(s) (HAF), While several clinical benefits of HAF are clearly evident, the basis for its anti-KS properties remains unknown. We investigated the a poptosis-inducing effects of HAF and the expression of apoptosis-related pr oteins in KS cells. Methods: KS Y-1 and KS SLK cells were treated with clin ical-grade crude preparations of hCG, recombinant hCG, or urine fractions e xhibiting anti-KS activity and then examined for features of apoptosis, Lev els of proteins associated with apoptosis were monitored by western blot an alysis, and cell DNA content was assessed by flow cytometry, Tumors induced in mice by inoculation of KS Y-1 cells were treated with preparations of h CG, and the tumors were examined for cell morphology and also for DNA fragm entation by use of the terminal deoxynucleotidyl transferase-mediated digox igenin-deoxyuridine triphosphate nick-end-labeling (TUNEL) assay. Results: The HAF present in some preparations of hCG and in urine fractions has the ability to induce apoptosis in KS cells in vitro and in vivo. HAF-triggered apoptosis was preceded by increased levels of the apoptosis-related protei ns c-Myc and c-Rel and cell accumulation in G(0)/G(1) phase of the cell cyc le. KS Y-1 cells transfected with a c-Myc complementary DNA showed elevated rates of apoptosis. Conclusion: The anti-KS activity of HAF appears to ind uce apoptosis, Such activity suggests a role for HAF in pregnancy-related r egulation of cell death.