Selective cytotoxic activities of two novel synthetic drugs on human breast carcinoma MCF-7 cells.
BACKGROUND
Breast cancer is the second leading cause of cancer deaths in US women. We evaluated two novel compounds, piperidinyl-diethylstilbestrol (DES) and pyrrolidinyl-diethylstilbestrol (DES) for cytotoxicity against brine shrimp larvae, MCF-7 and rat normal liver cells.


METHODS
In vivo cytotoxicity was evaluated against shrimp larvae for 24 h, while in vitro cell toxicity was evaluated by dye binding crystal-violet method after 48 h. The role of these compounds on different phases of the cell cycle was assessed by flow cytometry.


RESULTS
In shrimp assay, piperidinyl-DES and pyrrolidinyl-DES were potent with 50% effective dose (ED(50)) values of 7.9+/-0.38 and 15.6+/-1.3 microM, respectively. In MCF-7 and normal liver cells, the 50% lethal concentration (LC(50)) values were 19.7+/-0.95, 17.6+/-0.4 microM and 35.1 and >50 microM, respectively. Cell cycle analyses indicated that MCF-7 cells were arrested at the G(0)/G(1) stage with these compounds.


CONCLUSIONS
The results indicate that pyrrolidinyl-DES possesses highly selective, potent anticancer activity.
Badisa
Ramesh B
RB
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL-32307, USA.
Darling-Reed
Selina F
SF
Joseph
Patrick
P
Cooperwood
John S
JS
Latinwo
Lekan M
LM
Goodman
Carl B
CB
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001156:Artemia / Q000187:drug effects*; D001681:Biological Assay / Q000379:methods; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007814:Larva / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013267:Stilbenes / Q000138:chemical synthesis* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010880:Piperidines; D011759:Pyrrolidines; D013267:Stilbenes