1. Comparison of doxorubicin with cycloleucine in the treatment of sarcomas
E Knight, E D Savlov, J M MacIntyre, J Wolter Cancer Treat Rep . 1981 Jan-Feb;65(1-2):21-7.
In this patient series, doxorubicin and cycloleucine at a dose of 300 mg/kg both show response rates in the treatment of advanced soft tissue sarcomas of about 15%. Lower doses of cycloleucine (200 mg/kg) yielded less toxicity but were less effective against the sarcomas (6% response rate, three of 51 patients). There were no complete responses with cycloleucine and there were three with doxorubicin. Survival times for patients receiving doxorubicin were significantly longer than those of patients receiving cycloleucine at doses of 300 mg/kg (P less than 0.001) or 200 mg/kg (P = 0.02). The estimated survival times were 29 weeks for doxorubicin and 21 (300 mg/kg) and 18 (200 mg/kg) weeks for cycloleucine. Toxic effects due to cycloleucine were excessive, with severe thrombocytopenia and central nervous system depression being the most prominent.
2. Steady-state distribution of cycloleucine and alpha-aminoisobutyric acid between plasma and cerebrospinal fluid
D G Chain, H Davson, M T Shepherd, D J Begley, F O Briggs Exp Neurol . 1986 Jan;91(1):163-73. doi: 10.1016/0014-4886(86)90034-8.
Estimates of the steady-state distribution ratios of two nonmetabolizable amino acids, alpha-aminoisobutyric acid and aminocyclopentane carboxylic acid (cycloleucine), between plasma and cerebrospinal fluid were made with a view to establishing whether or not the low values found with metabolizable amino acids, such as glycine or leucine, could be accounted for by uptake and metabolism by the brain. The estimates, based on the ratios found after i.p. injections either in bolus form or by implantation of "osmotic pumps" containing the labeled amino acids, were comparable with those found for metabolizable amino acids.
3. Transcriptome analysis of the inhibitory effect of cycloleucine on myogenesis
Qinghua Nie, Zhijun Wang, Xing Ju, Danfeng Cai, Kan Li Poult Sci . 2022 Dec;101(12):102219. doi: 10.1016/j.psj.2022.102219.
N6-Methyladenosine (m6A) has been reported to involve and play an important role in various biological activities but seldom in poultry myogenesis. Cycloleucine usually functions as a nucleic acid methylation inhibitor, the inhibition efficiency of cycloleucine at the m6A level and corresponding dynamic changes of poultry muscle cells remain unknown. In this study, we aim to find out the effect of cycloleucine on the total N6-Methyladenosine level and its molecular mechanism for regulating myogenesis. A total of 745 differentially expressed genes (DEGs) were obtained by 10 mM, 20 mM, and 30 mM of cycloleucine treatment compared with 0 mM treatment. DEGs in 10 mM cycloleucine were significantly enriched in the biological process of skeletal muscle and satellite cell proliferation and differentiation, DEGs in 20 and 30 mM cycloleucine were enriched in some metabolic and biosynthetic processes. The trend analysis showed that 85% of all DEGs were significantly clustered into 4 files, among them 59% DEGs were dose-dependent and 26% were dose-independent, 52% DEGs were in downtrend and 33% DEGs were in uptrend. Also, the cycloleucine treatment could trigger cell cycle arrest in the G1 phase and depress myoblast cell proliferation and inhibit myotube formation. In conclusion, cycloleucine could continuously reduce the m6A level of myoblast cells, depress myoblast cell proliferation and inhibit myotube formation.
