| | |  | | | | Record from Web of Science® | | | | | | |
| CONCENTRATION-DEPENDENT DIFFERENCES IN THE MECHANISMS BY WHICH CAFFEINE POTENTIATES ETOPOSIDE CYTOTOXICITY IN HELA-CELLS |
|
|
| Author(s): LOCK RB, GALPERINA OV, FELDHOFF RC, RHODES LJ |
| Source: CANCER RESEARCH Volume: 54 Issue: 18 Pages: 4933-4939 Published: SEP 15 1994 |
| Times Cited: 75 References: 48 |
| Abstract: 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 G(2) arrest, enlarged cells appeared which contained evenly staining nuclear fragments, consistent with mitotic death. The methylxanthine, caffeine, enhanced cytotoxicity in a concentration-dependent manner,when applied for 24 h following etoposide exposure. One mM caffeine alleviated etoposide-induced G(2) arrest and increased the incidence of mitotic death, accounting for the potentiation of cytotoxicity. Brief caffeine exposures (5 or 10 mM for 1-2 h) caused specific tyrosine dephosphorylation and activation of p34(cdc2) kinase, and mitotic progression to a limited extent, in cells which were arrested in G(2) following etoposide treatment. However, longer exposure times at a high caffeine concentration (10 mM) caused inhibition of both cell cycle progression and mitotic death, and the enhancement of etoposide cytotoxicity could be accounted for by up to a 3-fold increase in the proportion of morphologically apoptotic cells. Thus, caffeine potentiates etoposide cytotoxicity by two morphologically distinct mechanisms depending on its concentration. |
| Document Type: Article |
| Language: English |
| Reprint Address: LOCK, RB (reprint author), UNIV LOUISVILLE, JAMES GRAHAM BROWN CANC CTR, DEPT MED, 529 S JACKSON ST, LOUISVILLE, KY 40292 USA |
Addresses:
1. UNIV LOUISVILLE, JAMES GRAHAM BROWN CANC CTR, DEPT BIOCHEM, LOUISVILLE, KY 40292 USA |
| Publisher: AMER ASSOC CANCER RESEARCH, PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 |
| Subject Category: Oncology |
| IDS Number: PF791 |
| ISSN: 0008-5472 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |