Morphological examination of HeLa cells exposed to etoposide for 1 h revealed two distinct modes of death: (a) within 6 h of drug removal, shrunken cells appeared which contained vacuolated cytoplasm and regions of intense chromatin staining, consistent with apoptosis; and (b) concomitant with release from G2 arrest, enlarged cells appeared which contained evenly staining nuclear fragments, con...

Effective chemotherapy remains a key issue for successful cancer treatment in general and neuroblastoma in particular. Here we report a chemotherapeutic strategy based on catalytic antibody-mediated prodrug activation. To study this approach in an animal model of neuroblastoma, we have synthesized prodrugs of etoposide, a drug widely used to treat this cancer in humans. The prodrug incorporates...

We have established several glioma-relevant oncogene-engineered cancer cells to reevaluate the oncogene-selective cytotoxicity of previously well-characterized anticancer drugs, such as etoposide, doxorubicin, staurosporine, and carmustine. Among several glioma-relevant oncogenes (activated epidermal growth factor receptor, Ras, and Akt, as well as Bcl-2 and p53DD used in the present study), th...

Cellular resistance to chemotherapeutic agents is attributable to several mechanisms, including alteration of topoisomerase IIalpha (topo IIalpha) gene expression. Etoposide-resistant MDA-VP human breast cancer cells express lower amounts of enzymatically active and drug-sensitive topo IIalpha than do MDA parent cells, suggesting that the low level of topo IIalpha is the mechanism of resistance...

Etoposide is one of the most successful chemotherapeutic agents used for the treatment of human cancers. The drug kills cells by inhibiting the ability of topoisomerase II to ligate nucleic acids that it cleaves during the double-stranded DNA passage reaction. Etoposide is composed of a polycyclic ring system (rings A-D), a glycosidic moiety at the C4 position, and a pendent ring (E-ring) at th...

BACKGROUND There are contradictory results from studies on the effect of curcumin, a plant phenolic compound with a well-established anticancer effect in vitro, on the action of etoposide in cancer cells. OBJECTIVE The aim of this study was to evaluate the influence of curcumin on the genotoxic and cytostatic action of etoposide in the LT12 cell line derived from BN rat acute myeloid leukemia...

From a single wild-type strain of Ehrlich ascites tumor, sublines resistant to daunorubicin, etoposide, and cis-diamminedichloroplatinum(II) have been developed in vivo. Different levels of resistance were achieved after 4 to 8 months for anthracyclines (greater than 32-fold), cis-diamminedichloroplatinum(II) (4-fold), and etoposide (greater than 6-fold). Anthracycline resistance was associated...

Lactoferrin (Lf) and folic acid (FA) were crosslinked on poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) for transporting etoposide across the blood-brain barrier (BBB) and treating human brain malignant glioblastoma. Lf- and FA-grafted PLGA NPs (Lf/FA/PLGA NPs) were employed to permeate the monolayer of human brain-microvascular endothelial cells (HBMECs) regulated by human astrocytes an...

Etoposide, a topoisomerase 2 (TOP2) inhibitor, is associated with the development of KMT2A (MLL)-rearranged infant leukemia. An epidemiological study suggested that in utero exposure to TOP2 inhibitors may be involved in generation of KMT2A (MLL) rearrangement. The present study examined the mechanism underlying the development of KMT2A (MLL)-rearranged infant leukemia in response to in utero e...

Etoposide protein binding in cancer patients is variable and has been related mathematically to a linear model consisting of serum albumin and total bilirubin [percentage unbound = (1.4 x total bilirubin) - (6.8 x albumin) + 34.4]. In this prospective evaluation of the model, plasma samples were obtained following the administration of etoposide in 31 patients, and the unbound percentage (% unb...