Combination of flavone acetic acid (FAA) with adriamycin, cis-platinum and difluoromethylornithine (DFMO) in vitro against human colon cancer cells.
Unresectable solid tumors in the metastatic stage are quite resistant to current chemotherapy and radiation therapy regimens. Flavone acetic acid (FAA) is a novel antitumor agent which appears to work through a different mechanism than the conventional chemotherapeutic agents. In preclinical studies it has shown effectiveness against a variety of transplantable murine and human tumors and appears to be solid tumor selective. It also has non-overlapping toxicities as compared to conventional agents. We therefore investigated FAA in vitro against human colon cancer cells and explored whether its effectiveness could be enhanced in combination with other agents such as adriamycin (ADR), cis-platinum (CP) and difluoromethylornithine (DFMO)--an inhibitor of polyamine biosynthesis. Addition of FAA for 24 hours in liquid media produced dose dependent growth inhibition. Using soft agar colony assay, growth was inhibited by 58% by 3mM FAA and only 1.4% by 0.375mM FAA. The combination of FAA and cis-platinum produced synergism at the lower doses tested. The combination of FAA and adriamycin produced antagonism at all doses tested and the combination of FAA with DFMO did not produce results significantly different from DFMO alone. We conclude that enhancement of FAA activity can be achieved in combination with conventional antitumor agents, but may be drug and dose specific.
Neelam
S S
SS
Department of Medicine, Wayne State University School of Medicine, Detroit, MI.
Bernabei
A
A
Freedland
C
C
Thompson
R
R
Corbett
T H
TH
Luk
G D
GD
D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D000518:Eflornithine / Q000008:administration & dosage; D005419:Flavonoids / Q000008:administration & dosage; D006801:Humans; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005419:Flavonoids; D004317:Doxorubicin; C049328:flavone acetic acid; D002945:Cisplatin; D000518:Eflornithine