Anti-tumor effect of chemically synthesized sulfolipids based on sea urchin's natural sulfonoquinovosylmonoacylglycerols.
We recently reported that 3'-sulfonoquinovosyl-1'-monoacylglycerol (designated A-5) extracted from sea urchin intestine was effective in suppressing the growth of solid tumors. Although the major fatty acid component of A-5 was a saturated C(16) acid, there were five other fatty acids, 14:0, 18:0, 14:1, 16:1, and 18:1, which constitute minor components of A-5. Therefore, it remains unclear as to which of these six fatty acid components of A-5 has the anti-tumor effect. In this study, we synthesized sulfolipids each containing only one of these six fatty acids and tested their cytotoxicity against tumor cells and in vivo anti-tumor effects on nude-mice bearing solid tumors of human lung adenocarcinoma cell line A-549. The IC(50) values of all products against tumor cells were more than 10(-5) M, suggesting weak cytotoxic activity compared with other chemotherapeutic compounds for cancer. On the other hand, in vivo anti-tumor assay showed that sulfoquinovosylmonoacylglycerols (SQMG) composed of 14:1 and 18:1 (designated SQMG(14:1) and SQMG(18:1), respectively) were significantly effective in suppressing the growth of solid tumors. Our data suggested that these two SQMGs had a substantial anti-tumor effect in vivo, and they are of interest as candidate drugs for anti-cancer treatment.
Sahara
Hiroeki
H
Marine Biomedical Institute, Sapporo Medical University School of Medicine, Oshidomari, Rishirifuji, Hokkaido 097-0101, Japan. ensho@sapmed.ac.jp
Hanashima
Shinya
S
Yamazaki
Takayuki
T
Takahashi
Shunya
S
Sugawara
Fumio
F
Ohtani
Seiji
S
Ishikawa
Masako
M
Mizushina
Yoshiyuki
Y
Ohta
Keisuke
K
Shimozawa
Kumiko
K
Gasa
Shinsei
S
Jimbow
Kouichi
K
Sakaguchi
Kengo
K
Sato
Noriyuki
N
Takahashi
Nobuaki
N
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic; D004305:Dose-Response Relationship, Drug; D005260:Female; D006017:Glycolipids / Q000138:chemical synthesis / Q000627:therapeutic use*; D006801:Humans; D008055:Lipids / Q000138:chemical synthesis / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050178:Monoglycerides; D009368:Neoplasm Transplantation; D012617:Sea Urchins / Q000737:chemistry; D014407:Tumor Cells, Cultured
C104118:3'-sulfonoquinovosyl-1'-monoacylglyceride; D000970:Antineoplastic Agents; D006017:Glycolipids; D008055:Lipids; D050178:Monoglycerides; C015518:sulfolipids