Induction of apoptosis in Kaposi's sarcoma spindle cell cultures by the subunits of human chorionic gonadotropin

AIDS. 1997 Sep;11(11):1333-40.

Abstract

Objectives: Elucidation of the mechanisms of the previously shown growth-inhibitory action of human chorionic gonadotropin (hCG) on Kaposi's sarcoma (KS) cells and the role of the luteinizing hormone/hCG receptor (hCGR).

Design and methods: Analysis of KS tissues and cultured spindle-type KS cells for the presence of the hCGR using 125I-hCG binding and reverse transcriptase-polymerase chain reaction; analysis of several hCG preparations (urinary, recombinant, isolated alpha and beta subunits); analysis of apoptosis mechanisms by several assays including using z-Val-Ala-Asp-fluoromethylketone (zVAD-FMK), a known apoptosis-inhibitory drug.

Results: First, we found that some urinary preparations of hCG (e.g., CG-10, Steris Profasi) were indeed KS-killing but others (such as Pregnyl, Choragon, Serono Profasi) were not. Secondly, recombinant subunits (alpha as well as beta) of hCG were KS cell-killing but recombinant intact hCG was not. Thirdly, the hCGR message and protein were undetectable in KS. Fourthly, CG10-induced cell death occurred by apoptosis and KS cells could be rescued by preincubation with zVAD-FMK. Finally, we also found that normal peripheral blood lymphocytes (PBL) were killed by CG-10.

Conclusion: It is proposed that the action of subunits or subunit fragments of hCG, mediated by a putative orphan receptor (as opposed to the hCGR) and executed by interleukin-1-converting enzyme (ICE)-like protease(s), constitutes a novel apoptosis mechanism effective towards KS cells, but PBLs and possibly other cells as well. These results provide a basis for testing in vitro the therapeutic efficacy of hCG preparations which, in turn, should improve current clinical trials with 'hCG' in patients who have KS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Anthracyclines*
  • Antibiotics, Antineoplastic / metabolism
  • Antibiotics, Antineoplastic / pharmacology
  • Apoptosis*
  • Flow Cytometry
  • Gonadotropins / immunology
  • Gonadotropins / metabolism*
  • Gonadotropins / pharmacology
  • HIV Infections / complications
  • HIV-1
  • Humans
  • Lymphocytes / drug effects
  • RNA, Messenger / metabolism
  • Receptors, LH / genetics
  • Receptors, LH / metabolism*
  • Receptors, LH / physiology*
  • Recombinant Proteins / metabolism
  • Sarcoma, Kaposi / metabolism*
  • Sarcoma, Kaposi / urine
  • Tumor Cells, Cultured
  • beta 2-Microglobulin / genetics
  • beta 2-Microglobulin / metabolism

Substances

  • Amino Acid Chloromethyl Ketones
  • Anthracyclines
  • Antibiotics, Antineoplastic
  • CG 10
  • Gonadotropins
  • RNA, Messenger
  • Receptors, LH
  • Recombinant Proteins
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • beta 2-Microglobulin