Antitumor effect of kigamicin D on mouse tumor models.
Kigamicin D is a novel anticancer agent that was identified using a new screening strategy that targets the tolerance of cancer cells to nutrient starvation [1, 2]. Oral administration of kigamicin D was previously described to show a strong antitumor effect in human tumor xenograft models of pancreatic tumors [2]. In this paper we describe that kigamicin D shows the same selective cytotoxicity against normal human cells such as lung fibroblast and prostate stromal cells under nutrient starved condition as against cancer cells. Kigamicin D inhibited tumor cell-induced angiogenesis in a dorsal air sac assay. On the basis of these results we tested other human tumor xenograft models and transplantable syngeneic tumor models in order to determine the spectrum of activity of kigamicin D against various cancers. Kigamicin D showed a weak antitumor effect against LX-1 and DMS-273 lung cancers, but had no effect on DLD-1 colon cancers. When tested against syngeneic tumors, kigamicin D showed a weak antitumor effect against colon26, but showed augmentation of tumor growth on IMC carcinoma at a broad dosage level. Kigamicin D does not show good antitumor activity against human xenograft tumors except pancreatic tumors and murine syngeneic tumors. We found that kigamicin D has excellent antitumor effect specific to pancreatic cancers. Surprisingly, high dosage of kigamicin D increased tumor growth of IMC carcinoma by than 200%. The phenomenon suggests that kigamicin D may cause some immunological response to the tumor.
Masuda
Toru
T
Numazu Bio-Medical Research Institute, Microbial Chemistry Research Center, 18-24 Miyamoto, Numazu-shi, Shizuoka 410-0301, Japan. masudat@bikaken.or.jp
Ohba
Shunichi
S
Kawada
Manabu
M
Osono
Michiyo
M
Ikeda
Daishiro
D
Esumi
Hiroyasu
H
Kunimoto
Setsuko
S
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010080:Oxazoles / Q000494:pharmacology / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D023041:Xenograft Model Antitumor Assays
D000903:Antibiotics, Antineoplastic; D010080:Oxazoles; C484110:kigamicin D; D004317:Doxorubicin