Antitumor effects of an antiangiogenic polysaccharide from an Arthrobacter species with or without a steroid.
A sulfated polysaccharide-peptidoglycan complex, DS-4152, isolated from the culture supernatant of an Arthrobacter species inhibited angiogenesis and tumor growth and enhanced the antiangiogenic activity of 11 steroid hormones by 2 to 100 times. In the presence of cortisone acetate or tetrahydro S, DS-4152 suppressed chick chorioallantoic membrane angiogenesis and murine tumor M5076 cell-induced s.c. angiogenesis. The antitumor effects of DS-4152 administered in combination with a steroid whose dose level did not affect tumor growth were examined. DS-4152 significantly inhibited the growth of s.c.-implanted B16 melanoma in combination with cortisone acetate. DS-4152 plus tetrahydro S inhibited the growth of s.c. solid tumors and prolonged the survival time of mice bearing highly metastasizing M5076. The body weight increase was not affected by any administration. On the other hand, the survival of mice with ascitic M5076 tumors was not affected by the combination of DS-4152 plus tetrahydro S. The antiangiogenic activity of DS-4152 was more potent than that of heparin. Furthermore, DS-4152 is an angiogenesis inhibitor by itself, without steroid hormones. Successive s.c. treatment with heparin caused hemorrhagic death, but with DS-4152, suppressed tumor growth without reducing body weight.
Tanaka
N G
NG
Research Institute, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Sakamoto
N
N
Inoue
K
K
Korenaga
H
H
Kadoya
S
S
Ogawa
H
H
Osada
Y
Y
D000818:Animals; D000970:Antineoplastic Agents; D001173:Arthrobacter; D002642:Chick Embryo; D004357:Drug Synergism; D051379:Mice; D009389:Neovascularization, Pathologic; D011135:Polysaccharides, Bacterial / Q000494:pharmacology*; D013256:Steroids / Q000494:pharmacology
D000970:Antineoplastic Agents; D011135:Polysaccharides, Bacterial; D013256:Steroids