Abstract | AIM: To explore the effect of atemoyacin-B (Ate) on overcoming multidrug resistance (MDR). METHODS:
Bullatacin (Bul) was used as a positive control. Cytotoxic effects of Bul and Ate were studied with cell culture of human MDR breast adenocarcinoma cells, MCF-7/Dox and human KBv200 cells, and their parental sensitive cell lines MCF-7 and KB. Cytotoxicity was determined by tetrazolium (MTT) assay. The function of P-glycoprotein (P-gp) was examined by Fura 2-AM assay. Cellular accumulation of doxorubicin (Dox) was determined by fluorescence spectrophotometry. Apoptosis was measured by flow cytometry. RESULTS: IC50 of Ate for MCF-7/Dox, MCF-7, KBv200, and KB cells were 122, 120, 1.34, and 1.27 nmol.L-1, respectively. IC50 of Bul for MCF-7/Dox, MCF-7, KBv200, and KB cells were 0.60, 0.59, 0.04, and 0.04 nmol.L-1, respectively. The cytotoxicities of Bul and Ate to MDR cells were similar to those to parental sensitive cells. Bul and Ate markedly increased cellular Fura-2 and Dox accumulation in MCF-7/Dox cells, but not in MCF-7 cells. The rates of apoptosis in MDR cells were similar to those in sensitive cells induced by Ate. CONCLUSION: There was no cross-resistance of P-gp positive MCF-7/Dox and KBv200 cell lines to Bul and Ate as compared with their sensitive P-gp negative MCF-7 and KB cell lines. The mechanism of the circumvention of MDR was associated with the decrease of P-gp function and the increase of cellular drug accumulation in MDR cells.
|
Authors | L W Fu, Q C Pan, Y J Liang, H B Huang |
Journal | Zhongguo yao li xue bao = Acta pharmacologica Sinica
(Zhongguo Yao Li Xue Bao)
Vol. 20
Issue 5
Pg. 435-9
(May 1999)
ISSN: 0253-9756 [Print] China |
PMID | 10678092
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Antineoplastic Agents, Phytogenic
- Fatty Alcohols
- Furans
- atemoyacin B
- bullatacin
- Doxorubicin
- 4-Butyrolactone
- Fura-2
|
Topics |
- 4-Butyrolactone
(analogs & derivatives, pharmacology)
- Adenocarcinoma
(pathology)
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
- Breast Neoplasms
(pathology)
- Doxorubicin
(metabolism)
- Drug Resistance, Multiple
- Drug Resistance, Neoplasm
- Fatty Alcohols
(pharmacology)
- Fura-2
(metabolism)
- Furans
(pharmacology)
- Humans
- KB Cells
(drug effects)
- Tumor Cells, Cultured
(drug effects)
|