Inhibition of proliferation on some neoplastic cell lines-act of carvedilol and captopril.
The present work examines the effects of beta and alpha1-adrenoceptor antagonist carvedilol, and angiotensin converting enzyme (ACE) inhibitor captopril, on in vitro growth of tumor cell lines derived from breast tumor (MDA-MB-361), melanoma (Fem-x), cervix adenocarcinoma (HeLa) and human myelogenous leukemia (K562). Carvedilol or captopril were applied on malignant cells at 0.1, 1, 5, 10 and 50 micromol. Cell survival was determined 48 hrs after drugs action by MTT. On all cell lines tested, carvedilol was a very potent inhibitor of cell proliferation. The order of sensitivity of various human cell lines to carvedilol's antiproliferative action was: myelogenous leukemia K562 (IC50 = 22.66 +/- 2.14 micromol), > cervix carcinoma HeLa (IC50 = 30.56 +/- 5.16 micromol), > melanoma Fem-x (IC50 = 32.17 +/- 5.75 micromol), > breast tumor MDA-MB-361 (IC50 = 35.04 +/- 2.95 micromol). In contrast, captopril, used in doses from 0.1-50 micromol, was ineffective (IC50 > 50 micromol) to the same cell lines. It is important to note that captopril in concentrations > 1 micromol led to a statistically significant increase in the percent of survived melanoma Fem-x cells (p < 0.05). Understanding the action of these established and clinically accepted agents could provide a basis for design of improved therapeutic regimens in the treatment of cancer diseases.
Stanojkovic
T P
TP
Dept. of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia and Montenegro. tanjast@lycos.com
Zizak
Z
Z
Mihailovic-Stanojevic
N
N
Petrovic
T
T
Juranic
Z
Z
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008856:Microscopy, Fluorescence; D011412:Propanolamines / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D002216:Captopril