Open AccessMenogaril, an Anthracycline Compound with a Novel Mechanism of Action: Cellular Pharmacology
Author(s) -
Wierzba Konstanty,
Sugimoto Yoshikazu,
Matsuo Kenichi,
Toko Toshiyuki,
Takeda Setsuo,
Yamada Yuji,
Tsukagoshi Shigeru
Publication year - 1990
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1990.tb02654.x
Subject(s) - anthracycline , mechanism of action , doxorubicin , dna , cytoplasm , cytotoxicity , in vitro , tubulin , cytoskeleton , cleavage (geology) , biology , biochemistry , intercalation (chemistry) , pharmacology , cell , microbiology and biotechnology , microtubule , chemistry , chemotherapy , genetics , paleontology , cancer , fracture (geology) , breast cancer , inorganic chemistry
Menogaril, an anthracycline compound possessing a significant antitumor activity after both po and iv administration, has been introduced into clinical trials. However, its mechanism of action has not been clarified yet. This study revealed that its cytotoxicity correlated very well with the inhibition of macromolecular synthesis, indicating the involvement of interaction with DNA. The spectrophotometric study showed a weaker binding of this compound to calf thymus DNA when compared to that of doxorubicin (adriamycin). Despite the lower binding affinity of menogaril to DNA, pronounced DNA cleavage was observed in an intact cell system, indicating that the character of the interaction with DNA is different from intercalation. In contrast to doxorubicin, menogaril is extensively localized in the cytoplasm. The cytoplasmic localization prompted us to study its effect on cytoskeleton proteins. It was found that menogaril inhibited the initial polymerization rate of tubulin, indicating a possible contribution of this process to the overall cytotoxicity of menogaril.