LOW-MOLECULAR-WEIGHT COMPONENTS BUT NOT DIMERIC HCG INHIBIT GROWTH AND DOWN-REGULATE AP-1 TRANSCRIPTION FACTOR IN KAPOSIS-SARCOMA CELLS

Kaposi's sarcoma, a sexually dimorphic disease inflicting high mortali ty in AIDS, remains at present without effective treatment. A recent r eport (Nature 375:64, 1995) showed that the placental glycoprotein hor mone, human chorionic gonadotropin (HCG), and surprisingly its beta su bunit, inhibit tumorigenicity and metastasis of Kaposi's sarcoma cells in mice xenografts. The anti-KS efficacy of a commercial HCG was subs equently demonstrated in clinical trials. Experimental data presented herein confirm that commercial HCG preparations (known to be about 25 % pure) display significant inhibitory action in a close-dependent man ner. However, pure and biologically active HCG has no effect on Kaposi 's sarcoma growth in culture. In fact, incubation of Kaposi's sarcoma cells with either one of four different well characterized preparation s of pure HCG dimer or any of its two subunits did not alter cellular proliferation suggesting that a contaminant (or degradation product) m ay be the active agent. Commercial HCG preparations were subfractionat ed based on molecular size and each fraction was tested with aspect to inhibition of KS cell growth, HCG radioreceptor binding and steroidog enic bioactivity. Results demonstrate that the anti-KS activity reside s among low molecular weight components, and not in bona fide (macromo lecular) HCG. Our study indicates that HCG activity and anti-KS action are separable. Interestingly, the active components in the crude HCG markedly down-regulate AP-1, a complex of transcription factors of the immediate-early response genes associated with cell growth. We conclu de that, as yet unidentified molecules, present in the commercial HCG preparations, are responsible for the growth inhibitory effects presum ably via the AP-1 signalling pathway.