Prevention of cancer cachexia by a novel nuclear factor {kappa}B inhibitor in prostate cancer.
OBJECTIVE
To investigate the association between serum interleukin-6 (IL-6) and cachexia in patients with prostate cancer and the inhibitory effect of a new nuclear factor kappaB (NF-kappaB) inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on IL-6 production and cachexia in an animal model of hormone-refractory prostate cancer.


METHODS
The association between serum IL-6 levels and variables of cachexia was evaluated in 98 patients with prostate cancer. The inhibitory effects of DHMEQ on IL-6 secretion and cachexia were investigated in in vitro and in vivo studies using JCA-1 cells derived from human prostate cancer.


RESULTS
Serum IL-6 levels were significantly elevated and cachexia developed in JCA-1 tumor-bearing mice as well as in prostate cancer patients with progressive disease. IL-6 secretion was significantly inhibited in JCA-1 cells exposed to DHMEQ. Intraperitoneal administration of DHMEQ (8 mg/kg) to tumor-bearing mice produced a significant amelioration of the reduction in body weight, epididymal fat weight, gastrocnemius muscle weight, hematocrit, and serum levels of triglyceride and albumin when compared with administration of DMSO or no treatment. DHMEQ caused a significant decrease of serum IL-6 level in JCA-1 tumor-bearing mice (all P < 0.05).


CONCLUSIONS
These results suggested an association between serum IL-6 and cachexia in patients with prostate cancer and in JCA-1 tumor-bearing mice and that a new NF-kappaB inhibitor, DHMEQ, could prevent the development of cachexia in JCA-1 tumor-bearing mice presumably through the inhibition of IL-6 secretion. DHMEQ seems to show promise as a novel and unique anticachectic agent in hormone-refractory prostate cancer.
Kuroda
Kenji
K
Department of Urology, Keio University, School of Medicine, Tokyo, Japan.
Horiguchi
Yutaka
Y
Nakashima
Jun
J
Kikuchi
Eiji
E
Kanao
Kent
K
Miyajima
Akira
A
Ohigashi
Takashi
T
Umezawa
Kazuo
K
Murai
Masaru
M
D000418:Albumins / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D015992:Body Mass Index; D001835:Body Weight; D002100:Cachexia / Q000517:prevention & control*; D045744:Cell Line, Tumor; D003512:Cyclohexanones / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006400:Hematocrit; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000150:complications* / Q000188:drug therapy*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D015431:Weight Loss / Q000187:drug effects
D000418:Albumins; D000970:Antineoplastic Agents; D001549:Benzamides; D003512:Cyclohexanones; D015850:Interleukin-6; D016328:NF-kappa B; D014280:Triglycerides; C464444:dehydroxymethylepoxyquinomicin