Activity of menogaril against various malignant lymphoma cell lines and a human lymphoma xenograft in mice.
Menogaril is an antitumor agent different from other anthracyclines in that it is active after oral administration; therefore, extravasation is not a side effect. In this basic study, we examined the antitumor activity of menogaril against malignant lymphoma. We compared its activity towards experimental malignant lymphoma with that of Adriamycin, epirubicin, pirarubicin, vincristine, and etoposide, treating mice with each drug at the dose schedule usually used for patients. Menogaril rapidly penetrated lymphoma cells and remained there at least 3 hours after the drug was washed out. Menogaril cleaved more double-stranded DNA in lymphoma cells than Adriamycin, epirubicin, pirarubicin, or etoposide. Menogaril had stronger antitumor activity against experimental malignant lymphoma in mice than Adriamycin, epirubicin, vincristine, and etoposide. Menogaril significantly lengthened the life span of mice bearing one of three lymphoma cell lines resistant to cisplatin, vincristine, or cyclophosphamide. Menogaril had stronger antitumor activity against the human malignant lymphoma xenograft LM-3 than Adriamycin. The strength of the cytotoxic activity of Menogaril might arise from its ready penetration into cells and its cleavage of double-stranded DNA. Therefore, Menogaril might become a useful drug for the treatment of patients with malignant lymphoma by oral administration; 7 days of administration was effective in the in vivo experiments.
Yoshida
M
M
Anticancer and Antimicrobials Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Fujioka
A
A
Nakano
K
K
Yuasa
C
C
Toko
T
T
Takeda
S
S
Unemi
N
N
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000627:therapeutic use; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000627:therapeutic use; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007940:Leukemia L5178 / Q000188:drug therapy / Q000378:metabolism; D007941:Leukemia P388 / Q000188:drug therapy / Q000378:metabolism; D008223:Lymphoma / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D017290:Menogaril / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D014183:Transplantation, Heterologous
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D005047:Etoposide; D004317:Doxorubicin; D017290:Menogaril