Anticancer drug resistance in drug‐induced cell death of U937 cells

Abstract

Cell death and subsequent post-mortem changes are integral parts of the normal development and maturation cycle. Cell death occurs by two alternative, opposite modes: apoptosis, a programmed form of cell death, and necrosis, an unordered and accidental form. Anticancer therapies take advantage from the ability of specific drugs to induce tumour cells to die. However, drug resistance is one of the main disadvantages in cancer chemotherapy. In the present work, we investigated the effect of taxol (paclitaxel), currently considered one of the most important anticancer drugs, on human monocytic leukemia U937 cells to verify drug-induced cell death (apoptosis) or anticancer drug-resistance. Taxol failed to induce U937 cells to apoptosis, thus showing a constitutive drug resistance of U937 cells for this substance; conversely, they were induced to a high rate of apoptosis by puromycin, cycloheximide or oxidative stress. The incubation of U937 cells with taxol simultaneously with puromycin resulted in a slight reduction of the apoptotic rate with respect to puromycin treatment alone. When cells were incubated with meta-iodobenzylguanidine (MIBG), another anticancer drug, alone or in combination with taxol and puromycin, only few morphological nuclear modifications were observed compared to untreated cells. Necrosis was, for all treatments, not higher than 8%.

Administration of cytoskeleton drugs during induction of apoptosis in U937 cells

“…In fact, neither CCB, nor colchine nor taxol were able to induce a significant rate of apoptotsis in U937 cells. In particular, with regard to taxol, U937 cells showed a resistance to the drug (Inoue et al, 2001;Abbro et al, 2004). Drug resistance to the anticancer agents that induce cell death through apoptosis or necrosis (Makin & Dive, 2001) is a fundamental problem in the chemotherapy treatment of most common human cancers.…”

Nucleoside antibiochemotherapy repressed the growth, chemoresistance, survival, and metastatic potentials of castration-resistant prostate cancer cells

“…For instance, gemcitabine was shown to mediate its antitumor effects by promoting apoptosis of malignant cells by blocking the progression of cells through the G1/S-phase boundary and also found to be beneficial when administered with docetaxel for treatment of mCRPC [27,28]. Furthermore, puromycin has both cytotoxic and antiproliferative effects, prompting us to investigate its ability to induce apoptosis and inhibit aggressive behaviors in mCRPCs [29].…”