methylselenocysteine
Also known as: Methylselenocysteine, MSC, Organoselenium compound, Methylated selenoamino acid derivative, Se-methylselenocysteine
Overview
Se-methylselenocysteine (MSC) is a naturally occurring organoselenium compound found in plants such as garlic, broccoli, and selenium-enriched yeast. It is a methylated derivative of selenocysteine, distinguished by its unique metabolic pathway. MSC is primarily investigated for its potential anticancer properties, particularly as an adjunct to chemotherapy, and for its antioxidant and chemopreventive effects. It is orally bioavailable and relatively stable, requiring enzymatic activation by β-lyase to release the active methylselenol metabolite. This metabolite is believed to mediate MSC's selective antiangiogenic and antitumor effects observed in preclinical models. While preclinical evidence for MSC is robust, human clinical data are limited, with most human studies on selenium focusing on other forms. MSC is currently under active investigation for its therapeutic potential, with ongoing research aiming to translate its promising preclinical findings into clinical applications.
Benefits
MSC demonstrates several evidence-based benefits, primarily in preclinical cancer models. It shows selective protection against organ-specific toxicity induced by chemotherapy, enhancing therapeutic efficacy without increasing adverse effects. This is supported by strong preclinical studies, indicating a significant improvement in tumor response and toxicity profiles. MSC is also a potent inhibitor of hypoxia-inducible factors (HIF-1α and HIF-2α) and downstream angiogenic factors like VEGF, leading to antiangiogenic effects and improved tumor drug delivery. This mechanism is well-supported by preclinical data. Furthermore, MSC exhibits potential chemopreventive effects through proapoptotic and antiproliferative mechanisms, promotion of DNA repair, and protection against oxidative stress. It may also prevent the development of chemotherapy resistance in preclinical models and possesses antioxidant properties that could protect normal tissues from oxidative damage. While these benefits are compelling in animal studies, human data are limited, and clear clinical significance, especially in selenium-replete populations, is not yet established.
How it works
Se-methylselenocysteine (MSC) exerts its biological effects primarily after being metabolized by the enzyme β-lyase, which converts it into methylselenol. This active metabolite then modulates several key anticancer pathways. Methylselenol inhibits hypoxia-inducible factors (HIF-1α and HIF-2α), which are crucial for tumor angiogenesis and growth, leading to a reduction in vascular endothelial growth factor (VEGF) and subsequent antiangiogenic effects. It also modulates other inflammatory and proliferative pathways by inhibiting COX-2 and inducible nitric oxide synthase (iNOS). Furthermore, MSC interacts with the tumor microenvironment by normalizing vasculature and reducing interstitial fluid pressure, which can enhance the delivery and efficacy of chemotherapeutic agents. Its antioxidant properties contribute to protecting normal tissues from oxidative damage. MSC's high oral bioavailability and distinct pharmacokinetics, with less incorporation into proteins compared to selenomethionine, allow for more direct and targeted action.
Side effects
The overall safety profile of Se-methylselenocysteine (MSC) appears to be generally well tolerated in preclinical and limited clinical studies, with no significant toxicity reported at therapeutic doses in animal models. Common, uncommon, or rare side effects are not well documented in humans due to the limited number of clinical trials. Animal studies have reported minimal toxicity. There are potential interactions with chemotherapeutic agents, as MSC may modulate their efficacy and toxicity profiles; however, this requires further clinical validation. Contraindications are not well established, but caution is advised in selenium-replete individuals, as studies have shown no clear pharmacodynamic effects in this population, and there is a theoretical risk of selenium toxicity if combined with other selenium sources. The effects of MSC may differ between selenium-deficient and selenium-replete populations, with observed differences in pharmacokinetics but no clear clinical benefit demonstrated in selenium-replete men. Comprehensive safety data from large-scale human trials are still needed.
Dosage
Optimal dosage ranges for Se-methylselenocysteine (MSC) are not clearly established in humans. Preclinical studies have utilized doses that correspond to plasma selenium concentrations around 15 μM, which are significantly higher (approximately 72-fold) than typical chemoprevention doses of selenomethionine. The maximum safe dose for MSC in humans is not well defined, although related selenium compounds have been tolerated at high doses in clinical settings with monitoring. Sustained dosing appears to be required to achieve and maintain therapeutic plasma levels, and the timing of administration relative to chemotherapy may influence its efficacy. MSC is preferred over selenomethionine for its potential therapeutic anticancer effects due to its direct conversion to methylselenol and less incorporation into proteins, which may lead to more targeted action. It exhibits high oral bioavailability, and its absorption is not significantly impacted by cofactors, though β-lyase enzyme activity is required for its activation within the body.
FAQs
Is MSC safe to use as a supplement?
Preclinical data suggest good safety for MSC, and limited human studies have not reported major safety concerns at the doses investigated. However, more extensive human trials are needed to fully establish its safety profile.
Does MSC prevent cancer in humans?
Current evidence is insufficient to conclude that MSC prevents cancer in humans. While preclinical studies are promising, human trials with other selenium forms have not shown clear cancer prevention benefits in selenium-replete populations.
Can MSC be used with chemotherapy?
Preclinical studies indicate that MSC may enhance chemotherapy efficacy and reduce toxicity. However, clinical trials are necessary to confirm these benefits and establish safe and effective co-administration protocols in humans.
How quickly does MSC work?
In preclinical models, effects of MSC are observed with sustained dosing. Human pharmacodynamics are not yet clear, so the exact time frame for clinical effects remains undefined.
Is MSC better than other selenium forms?
MSC may offer advantages due to its direct activation to methylselenol and antiangiogenic properties, which differ from other selenium forms. However, its clinical superiority over other selenium compounds is currently unproven and requires further research.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3974093/ – This preclinical animal study demonstrated that Se-methylselenocysteine (MSC) selectively protects against chemotherapy-induced toxicity while enhancing antitumor efficacy. The research highlighted MSC's ability to inhibit HIF-1α/2α and VEGF, confirming its antiangiogenic properties and oral bioavailability in animal models.
- https://www.oncotarget.com/article/15460/text/ – This randomized, double-blind clinical trial in 29 selenium-replete men investigated the pharmacokinetics of MSC versus selenomethionine. It found distinct pharmacokinetic profiles for MSC but observed no significant pharmacodynamic effects on selenoproteins or toxicity, suggesting different metabolic pathways and potential for targeted action.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC3111097/ – This review, incorporating preclinical data, positions MSC as a promising antiangiogenic agent. It emphasizes MSC's requirement for β-lyase activation and its stability and effectiveness in various preclinical cancer models, underscoring its potential for future clinical applications.
- https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0026259 – This systematic review and meta-analysis explored the role of selenium in cancer prevention, particularly lung cancer in individuals with low selenium status. While it included various selenium forms, it noted the proapoptotic and antiproliferative effects of selenium compounds, including MSC, in preclinical studies, though specific human data on MSC were limited.