G. Carles et al., MODIFICATION OF THE ACTION OF PACLITAXEL ON A HUMAN DIFFERENTIATED COLON-CANCER CELL-LINE AFTER LONG-TERM PRETREATMENT AT VERY-LOW DOSE, Bulletin du cancer, 83(2), 1996, pp. 135-138
Taxoids (paclitaxel, Taxol(R) and docetaxel, Taxotere(R)), drugs which
stabilize microtubules, demonstrate marked activity against ovarian,
brain and lung cancer We investigated, on the human colon adenocarcino
ma HT29-D4 cell line, firstly the effects of taxoids in function of th
e differentiation state and secondly the effects of a low dose of pacl
itaxel on the differentiation process. The cellular parameters studied
were microtubular network, cell cycle and cell tubulin content. Undif
ferentiated cells treated with paclitaxel or docetaxel (10-100 nM) cla
ssically induced bundles in interphasic cells and pseudoasters in mito
tic cells, arrest in cell cycle in G(2)M and increase in tubulin conte
nt. Inversely, no modification was observed in differentiated cells af
ter similar taxoid treatment. Long-term low-dose pretreatment of diffe
rentiated cells restitutes some sensitivity to taxoids since these cel
ls become responsive to further taxoid treatment, as reflected by modi
fications of the microtubule network.