TY - JOUR
T1 - Menogaril, an Anthracycline Compound with a Novel Mechanism of Action
T2 - Cellular Pharmacology
AU - Wierzba, Konstanty
AU - Sugimoto, Yoshikazu
AU - Matsuo, Ken‐ichi ‐i
AU - Toko, Toshiyuki
AU - Takeda, Setsuo
AU - Yamada, Yuji
AU - Tsukagoshi, Shigeru
PY - 1990/8
Y1 - 1990/8
N2 - 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.
AB - 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.
KW - Anthracycline compound
KW - Interaction with DNA
KW - Menogaril
KW - Microtubular system
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U2 - 10.1111/j.1349-7006.1990.tb02654.x
DO - 10.1111/j.1349-7006.1990.tb02654.x
M3 - Article
C2 - 2144516
AN - SCOPUS:0025046376
SN - 1347-9032
VL - 81
SP - 842
EP - 849
JO - Cancer Science
JF - Cancer Science
IS - 8
ER -
