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E J Modest

Publications and source records attributed to E J Modest.

75 records · Page 5Linked to original sources
PubMedDate not supplied

Cell kill and cytostasis by ET-18-OCH3 and heat.

BACKGROUND: The ether lipid analogue 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) is known to have plasma membrane interacting antitumor activity. However, the mechanism and the mode of action of its activity remain to be elucidated fully. MATERIALS AND METHODS: In this study, the proportion of the inhibitory effects resulting either from direct cell kill or from cytostasis induced by (ET-18-OCH3) alone or in combination with heat in BG-1 human ovarian carcinoma cells was quantitated. RESULTS: The magnitude of both cell kill and cytostasis in BG-1 cells was dependent on the concentration of ET-18-OCH3 and the duration of exposure. Cell kill induced by exposure to 2 or 8 microM ET-18-OCH3 for 1-14 days could be expressed as a simple exponential function of exposure dose (concentration x time). As assayed by colony formation, cell survival after continuous exposure to the drug was significantly reduced from that measured when the drug was removed and the cells were incubated for 14 days in drug-free medium. CONCLUSIONS: We conclude that ET-18-OCH3 induces substantial cytostasis as well as cell kill in BG-1 cells and that this cytostasis is directly proportional to the amount of cell kill induced. These data are important in determining appropriate treatment regimens using ET-18-OCH3, either alone or in combination with other anticancer agents.

Antineoplastic Agents↗
PubMedDate not supplied

Effects of structural modifications of ether lipids on antiproliferative activity against human glioma cell lines.

The effect of structural modifications of ether lipids on antiproliferative activity was studied in four human glioma cell lines. Drug potency, determined by microtetrazolium assay, varied 7- to 30-fold. CP 46,665 was most potent; Amido-18-OEt was least potent. Antiproliferative activity was highly dependent on drug exposure time. Except for CP 46,665, which reached maximal activity after 2 hr, 40 microM ether lipids were effective only after 24 hr. Structural modifications of ether lipids can increase their potency and reduce the time required for antiproliferative activity. Ether lipid analogs may be useful for treating human gliomas.

Antineoplastic Agents↗
PubMedDate not supplied

Cytokinetic and morphologic differences in ovarian cancer cells treated with ET-18-OCH3 and the DNA-interacting agent, etoposide.

New antineoplastic agents with different cytotoxic mechanisms are of interest for their ability to overcome resistance to conventional DNA-interacting agents. Ether lipids are known to be active against ovarian carcinoma both in vitro and in vivo, and the cell membrane is believed to be the target of their antitumor activity. In this study we have investigated the different cytokinetic and morphologic responses of human ovarian carcinoma cells (BG-1) to one of the ether lipids (ET-18-OCH3) and to etoposide. Etoposide induced a significantly greater G2/M block. However, the proportion of the cycling cell fraction decreased significantly in cells treated by ET-18-OCH3 and induction of the hypodiploid traction was strongly correlated with reduction of the cycling cell fraction. On the other hand, the hyperdiploid fraction was found to correlate with reduction of the cycling cell fraction in etoposide treated cells. Despite the significant appearance of the hypodiploid fraction, apoptosis was not observed by DNA-gel assay. Microscopic study showed that the hyperdiploid fraction represented cells with multiple nuclei. These observations support the unique lethal effect of ET-18-OCH3 on ovarian carcinoma cells, distinguishing it from the action of a typical DNA-interacting agent. The membrane-targeted ether lipids deserve consideration for the future chemotherapy of ovarian carcinoma, perhaps in combination with the appropriate DNA-interacting agent. New antineoplastic agents with different cytotoxic mechanisms are of interest not only for their unique inhibitory properties but also for their potential of overcoming resistance to conventional DNA-interacting agents. Ether lipids are known to be active against ovarian carcinoma both in vitro (1, 2, 3) and in vivo (4, 5), and the cell membrane is believed to be the target of their antitumor activity. Etoposide, a DNA-interacting agent, is also active against human ovarian cancer cells in vitro (6) or in clinical trials either as a single agent (7) or in combination with cisplatin (8). We have reported that a cytotoxic dose of one of the ether lipids, ET-18-OCH3, induces a G2/M block in BG-1 human ovarian cancer cells, and also a hypodiploid fraction as shown on DNA analysis by flow cytometry (FCM) (9). The G2/M block was also observed in BG-1 cells following etoposide treatment (6). In the present study, we have investigated the differences in the cytokinetic and morphologic responses of BG-1 cells to ET-18-OCH3 and to etoposide.

Antineoplastic Agents↗