The Benefits and Safety of Se-Methylselenocysteine

Se-Methylselenocysteine is a naturally occurring compound of selenium, and is synthesized by plants such as broccoli and garlic. Selenium is an essential micronutrient for your body, incorporated into enzymes and other proteins to create antioxidant enzymes called selenoproteins, which can help block cellular damage from free radicals.

Anti-carcinogenic properties ^[1-2]

Se-methylselenocysteine (MSC) is a naturally occurring selenium compound that has very favorable pharmacokinetic properties with high peroral bioavailability in humans. MSC has been proven to have a chemo-preventive property, which is shown by several authors via various cell culture models and animal models. It is also shown to have anti-carcinogenic properties via inducing cell cycle arrest and inducing apoptotic cell death. 

Se-methylselenocysteine (MSC) was a monomethylated selenine analogue, which could convert into methylselenol by selenocysteine conjugated β-lyase. The potency of MSC depends entirely on the production of the active metabolite methylselenol. In the micromolar range, MSC showed cytotoxic effects against many human cancer cell lines including melanoma, colon, breast and oral squamous cancer cells (IC50 = 54, 632.8, 193 and 50 μM, respectively). In addition, MSC could synergistically enhance the anti-tumor efficacy of chemotherapeutic agents in vivo.

Reduce drug toxicity^[3]

Se-methylselenocysteine significantly protected against organ-specific toxicity induced by lethal doses of cyclophosphamide, cisplatin, oxaliplatin, and irinotecan. These include diarrhoea, stomatitis, alopecia, bladder, kidney, and bone marrow toxicities. Protection from lethal toxicity by MSC was associated with enhanced antitumour activity in rats bearing advanced Ward colorectal carcinoma and in nude mice bearing human squamous cell carcinoma of the head and neck, FaDu, and A253 xenografts.

Se-methylselenocysteine offers selective protection against organ-specific toxicity induced by clinically active agents and enhances further antitumour activity, resulting in improved therapeutic index. These data provided the rationale for the need to clinically evaluate MSC as selective modulator of the antitumour activity and selectivity of anticancer drugs.

Safety^[4]

A study from Hui Yang and Xudong Jia evaluated the safety of Se-methylselenocysteine and provide the Acceptable Daily Intake (ADI) for its use in human diet. Our results demonstrated that SeMC, with the Median Lethal Dose (LD50) of 12.6 and 9.26 mg/kg BW in female and male mice, was of high potent of health hazard under acute oral exposure, but a battery of tests including Ames test, micronucleus assay and mouse sperm malformation assay suggested that SeMC was not genotoxic. The repeated dose study indicated little systemic toxicity of SeMC at supernutritional levels (0.5, 0.7, 0.9 mg/kg BW/day) after 90-day oral exposure. Importantly, the 95% lower confidence value of Benchmark Dose (BMDL) was estimated as 0.34 mg/kg BW/day according to the elevated relative liver weight. The ADI for human was established at 3.4 μg/kg BW/day. The results suggested greater safety of SeMC as a nutritional selenium supplement, but health risk needs to be further evaluated when SeMC is applied beyond this level to achieve cancer chemoprevention.

References

[1] Chapter Two - Methods for accurate and reproducible studies of pharmacological effects of selenium in cancer. Methods in Enzymology. Volume 662, 2022, Pages 25-62.

[2] Small molecule selenium-containing compounds: Recent development and therapeutic applications. European Journal of Medicinal Chemistry. Volume 223, 5 November 2021, 113621.

[3] Cao, S., Durrani, F., Tóth, K. et al. Se-methylselenocysteine offers selective protection against toxicity and potentiates the antitumour activity of anticancer drugs in preclinical animal models. Br J Cancer 110, 1733–1743 (2014).

[4] Safety evaluation of Se-methylselenocysteine as nutritional selenium supplement: Acute toxicity, genotoxicity and subchronic toxicity. Regulatory Toxicology and Pharmacology. Volume 70, Issue 3, December 2014, Pages 720-727.

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