Hierarchy of carcinoma cell responses to apigenin: gap junctional coupling versus proliferation.
We discriminated the role of gap junctional communication and phenotypic constitution of tumour cells in determining their responsiveness to apigenin. Effects of apigenin on intercellular communication and proliferation of two lines of carcinoma cells, uncoupled HeLa cells and their coupled Cx43-transfected counterparts, were analysed and compared with the responses of highly coupled BICR/M1Rk cells. Dye transfer analyses demonstrated that apigenin decreases the degree of coupling in Cx43-coupled populations of HeLa cells but does not affect BICR/M1Rk cells. Similarly, no communication enhancement was observed in originally uncoupled HeLa cell populations. A G2-specific growth arrest paralleled by the induction of apoptosis was observed which was more pronounced and correlated with higher number of apoptotic events in coupled HeLa Cx43 transfectants than in parental cell line. On the other hand, apoptosis was not observed in highly coupled BICR/M1Rk cells, instead, these cells were only transiently blocked in G2 which might be a result of their ability to metabolise apigenin. These data demonstrate a hierarchy of systems determining cellular sensitivity to apigenin. Gap junctional coupling does not influence the quality of cell cycle-related responses to apigenin but modulates their magnitude. This modulating effect of gap junctional coupling depends, however, on a cellular context determined by specific cell phenotype and can be overcome by tissue-specific compensatory mechanisms.
Czyz
Jaroslaw
J
Department of Cell Biology, Faculty of Biotechnology, Jagiellonian University, 30-387 Cracow, Poland. jaro@mol.uj.edu.pl
Irmer
Uwe
U
Zappe
Claudia
C
Mauz
Matthias
M
Hülser
Dieter F
DF
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D047310:Apigenin / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division; D045744:Cell Line, Tumor; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D005452:Fluoresceins / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051381:Rats; D014162:Transfection
D000970:Antineoplastic Agents; D018031:Connexin 43; D005452:Fluoresceins; D047310:Apigenin; C007740:fluorexon