Docetaxel-induced apoptosis in the mitotic phase: electron microscopic and cytochemical studies of human leukemia cells

Abstract

We induced apoptosis in cells of the human leukemia cell line HL-60 using an antitumor agent, docetaxel (Taxotere), and investigated apoptosis in various aspects using in situ end-labeling (ISEL) of DNA, DNA fragmentation assay, flow cytometry, and electron microscopy. Because it inhibits depolymerization of tubulin, docetaxel is thought to arrest the cell cycle at the mitotic stage and to exert an antitumor effect. In this study, accumulation of docetaxel-treated cells at the G2/M phase was detected using flow cytometry. On ISEL of DNA, DNA fragmentation was observed at the mitotic stage. On electron microscopy, the nuclei of apoptotic cells lost their nuclear membranes, as do cells at mitosis, demonstrating that the cells were arrested mainly at the M phase in the cell cycle.

Luteinizing hormone-releasing hormone receptor–targeted deslorelin-docetaxel conjugate enhances efficacy of docetaxel in prostate cancer therapy

“…Docetaxel induced microtubule damage results in a marked and prolonged G 2 -M arrest and subsequent apoptosis (40). Flow cytometric analysis of docetaxel-treated cells therefore exhibits an increase in the number of cells in the G 2 -M phase, suggesting a G 2 -M block and an increase in sub-G 0 -G 1 phase, indicating the hypodiploid or apoptotic cells.…”

Phase II Trials of Imatinib Mesylate and Docetaxel in Patients with Metastatic Non-small Cell Lung Cancer and Head and Neck Squamous Cell Carcinoma

“…First, antagonism between imatinib and docetaxel may occur because imatinib mesylate may arrest tumor cells at the G 0 -G 1 checkpoint through inhibition of PDGFR␣ and the downstream PI3K/AKT pathway 31 ; this may compromise the antitumor effects of docetaxel, which works during M phase. 32,33 Second, p-glycoprotein (MDR-1), an ATP-binding cassette (ABC) transport protein B1, has both docetaxel and imatinib as substrates and is implicated in resistance to both agents. 34,35 The ABCB1 gene is strongly induced by docetaxel in resistant A549 cell lines 35 possibly through activation of pregnane X receptor pathway 36 ; and imatinib resistance has also been linked to ABCB1 induction in leukemic cell lines.…”

Involvement of microRNA-21 in mediating chemo-resistance to docetaxel in androgen-independent prostate cancer PC3 cells

“…Docetaxel is the standard of care for men diagnosed with AIPC [1] . Docetaxel binds to the β-tubulin subunit, causing stabilization of microtubules, which leads to mitotic arrest and subsequent apoptosis [2] . Docetaxel has been administered to men with AIPC in clinical trials, where it has been found to prolong survival in men with this disease [3] .…”