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.
Ademetionine（S-Adenosyl methionine；AdoMet；SAMe）是一种内源性分子，由蛋氨酸和ATP在蛋氨酸腺苷转移酶的作用下产生，作为主要的甲基供体在细胞代谢中起重要作用[1]。Ademetionine可用作治疗抑郁症、肝脏疾病、纤维肌痛和骨关节炎的药物[2]。Ademetionine还可作为膳食补充剂，支持骨骼和关节健康以及情绪健康[3]。
在体外，Ademetionine（300µM）处理头颈部鳞状癌细胞系（Cal-33和JHU-SCC-011）24或48h，诱导了G1期和G2/M期细胞群分别从44.6%下降到28.4%和从14.7%下降到7.6%，同时S期细胞群从36.1%显著增加到61%，减弱了细胞周期进程，还抑制了细胞迁移[4]。Ademetionine（500µM）处理三阴性人乳腺癌细胞系（MDA-MB-468 和 MDA-MB-231）24或48h，上调了细胞内miR-34c和miR-449a的表达，促进了细胞凋亡[5]。
在体内，Ademetionine（30mg/kg）通过口服治疗丙戊酸诱发的类似自闭症行为的小鼠3天，阻止了病症的发展，并使前额叶皮层的氧化还原电位正常化[6]。Ademetionine（100mg/kg）通过口服治疗戊四唑诱导的癫痫大鼠，延长了癫痫发作潜伏期，降低了癫痫发作严重程度评分[7]。