Ponalrestat, an aldose reductase inhibitor, inhibits cachexia syndrome in nude mice bearing human melanomas G361 and SEKI.
Our recent study has demonstrated that ponalrestat, an aldose reductase inhibitor, activates lipoprotein lipase (LPL) activity in the adipose tissue and alleviates the cachectic symptoms induced by B16 melanoma in mice. In this study, the effect of ponalrestat on cachexia symptoms in nude mice bearing human melanomas G361 and SEKI was investigated because it has been suggested that the suppression of LPL has an important role in cachexia induction by these two melanomas in nude mice. Mice bearing G361 subcutaneously did not gain weight and became cachectic, associated with the tumor growth. Tumor growth was not affected by ponalrestat, nevertheless treatment with ponalrestat resulted in an amelioration of the reduction in the weight of body mass, epididymal fat, gastrocnemius muscle, carcass and whole body lipid induced by the presence of G361. A severe weight loss observed in nude mice bearing SEKI was also partially attenuated by ponalrestat treatment. Overall, this study showed that ponalrestat is effective in the attenuation of the cachectic symptoms induced by human melanomas G361 and SEKI in nude mice, suggesting that ponalrestat has a potential usefulness for the treatment of cancer cachexia.
Kawamura
I
I
Department of Metabolic Diseases, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan. ikuokawamura@po.fujisawa.co.jp
Lacey
E
E
Inami
M
M
Nishigaki
F
F
Naoe
Y
Y
Tsujimoto
S
S
Manda
T
T
Goto
T
T
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004822:Epididymis / Q000187:drug effects; D006131:Growth Inhibitors / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis; D008297:Male; D008545:Melanoma / Q000150:complications* / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018482:Muscle, Skeletal / Q000187:drug effects; D009368:Neoplasm Transplantation; D010793:Phthalazines / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D010793:Phthalazines; C042829:ponalrestat; D000449:Aldehyde Reductase