Ademetionine

Ademetionine (S-Adenosyl methionine; AdoMet; SAMe) is an endogenous molecule generated from methionine and ATP by the action of methionine adenosyltransferase and plays an important role in cellular metabolism as the main methyl donor ^[1]. Ademetionine can be used as a drug to treat depression, liver disease, fibromyalgia and osteoarthritis ^[2]. Ademetionine can also be used as a dietary supplement to support bone and joint health and emotional health ^[3].

In vitro, ademetionine (300µM) treatment of head and neck squamous cell carcinoma cell lines (Cal-33 and JHU-SCC-011) for 24 or 48h induced a decrease in the G1 phase and G2/M phase cell populations from 44.6% to 28.4% and from 14.7% to 7.6%, respectively, while the S phase cell population increased significantly from 36.1% to 61%, attenuated cell cycle progression, and inhibited cell migration ^[4]. Ademetionine (500µM) treatment of triple-negative human breast cancer cell lines (MDA-MB-468 and MDA-MB-231) for 24 or 48h upregulated the expression of intracellular miR-34c and miR-449a and promoted cell apoptosis^[5].

In vivo, oral treatment of mice with valproate-induced autistic-like behavior with ademetionine (30mg/kg) for 3 days prevented the development of symptoms and normalized the redox potential of the prefrontal cortex^[6]. Oral treatment of rats with pentylenetetrazol-induced epilepsy with ademetionine (100mg/kg) prolonged the latency period of epileptic seizures and reduced the severity score of epileptic seizures^[7].

References:
[1] Brula M, Cupp M J, Tracy T S. SAMe (S-adenosyl-l-methionine)[M]//Dietary Supplements: Toxicology and Clinical Pharmacology. Totowa, NJ: Humana Press, 2003: 321-334.
[2] Lu S C, Mato J M. S-adenosylmethionine in liver health, injury, and cancer[J]. Physiological reviews, 2012, 92(4): 1515-1542.
[3] Najm W I, Reinsch S, Hoehler F, et al. S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial.[ISRCTN36233495][J]. BMC musculoskeletal disorders, 2004, 5: 1-15.
[4] Mosca L, Minopoli M, Pagano M, et al. Effects of S-adenosyl-L-methionine on the invasion and migration of head and neck squamous cancer cells and analysis of the underlying mechanisms[J]. International Journal of Oncology, 2020, 56(5): 1212-1224.
[5] Coppola A, Ilisso C P, Stellavato A, et al. S-Adenosylmethionine inhibits cell growth and migration of triple negative breast cancer cells through upregulating MiRNA-34c and MiRNA-449a[J]. International Journal of Molecular Sciences, 2020, 22(1): 286.
[6] Ornoy A, Weinstein-Fudim L, Tfilin M, et al. S-adenosyl methionine prevents ASD like behaviors triggered by early postnatal valproic acid exposure in very young mice[J]. Neurotoxicology and teratology, 2019, 71: 64-74.
[7] Dhediya R M, Joshi S S, Gajbhiye S V, et al. Evaluation of antiepileptic effect of S-adenosyl methionine and its role in memory impairment in pentylenetetrazole-induced kindling model in rats[J]. Epilepsy & Behavior, 2016, 61: 153-157.