Antineoplastic activity of idazoxan hydrochloride.
OBJECTIVE
Idazoxan hydrochloride (IDA) is a 241 molecular weight imidazoline and adrenoreceptor ligand. It binds to mitochondrial membranes and promotes apoptosis of pancreatic beta cells. Since IDA has not been tested against tumor cells, the purpose of our study was to determine if IDA has antineoplastic activity.


METHODS
We used the conversion of a soluble tetrazolium salt to an insoluble formazan precipitate and differential staining cytotoxicity assays to determine if IDA was cytotoxic to cell lines of murine lung cancer and human prostate cancer, as well as to a variety of fresh human tumor samples. We used flow cytometry to analyze cell death and calreticulin expression.


RESULTS
IDA is cytotoxic to both cell lines and against aliquots of specimens of breast, gastric, lung, ovarian and prostate cancers as well as non-Hodgkin's lymphoma. It produces apoptotic cell death and promotes calreticulin expression, suggesting that IDA might be immunomodulatory in vivo.


CONCLUSIONS
We anticipate that IDA will be clinically useful in cancer treatment.
Eilon
G F
GF
Long Beach, CA, USA.
Weisenthal
L
L
Stupecky
M
M
Landucci
G
G
Slater
L M
LM
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D037282:Calreticulin / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019329:Idazoxan / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009369:Neoplasms / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured
D017304:Annexin A5; D000970:Antineoplastic Agents; D037282:Calreticulin; D019329:Idazoxan