Different apoptotic responses and patterns in adhering and floating neoplastic cell cultures: effects of microtubule antagonists.
The relationship between apoptotic progression and cell cycle perturbation induced by microtubule-destabilising (vinblastine, Colcemid) and -stabilising (taxol) drugs was studied in two mesenchyme-derived neoplastic cell lines, growing as suspension (Jurkat) and monolayer (SGS/3A) culture, by morphocytochemical and biochemical approaches. The same kind of drug induced different effects on the cell kinetics (proliferation, polyploidisation, death) of the two cell lines. In floating cells, the drugs appeared more effective during the S phase, while in adherent cells they were more effective during the G2/M phase. Moreover two distinct neoplasia-associated apoptotic phenotypes emerged: the first pattern was the typical one and was found in cells with a low transition through the S/G2 phase (Jurkat), and the second one was mainly characterised by a cell death derived from micronucleated and mitotic cells, as a consequence of a low transition through the M/G1 phase (SGS/3A). Our data show that the machinery required for the trigger and progression of apoptosis is present in every cell cycle phase, also in conditions of karyological alterations (aneugenic micronucleations). On the other hand, a different sensitivity of the two microtubular components (interphasic network and mitotic spindle) appears to be related to the anchorage-dependence or -independence during the cell growth disturbances after exposure to antimicrotubular drugs.
Sciola
Luigi
L
Department of Physiological, Biochemical and Cellular Sciences, University of Sassari, Via Muroni 25, 07100 Sassari, Italy. sciola@ssmain.uniss.it
Spano
Alessandra
A
Monaco
Gianni
G
Bottone
Maria Grazia
MG
Barni
Sergio
S
D024422:Aneugens / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D004247:DNA / Q000032:analysis; D053938:DNA Fragmentation; D003703:Demecolcine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells; D008870:Microtubules / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D014747:Vinblastine / Q000494:pharmacology
D024422:Aneugens; D014747:Vinblastine; D004247:DNA; D017239:Paclitaxel; D003703:Demecolcine