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Comparison of selenium and sulfur analogs in cancer prevention
1Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263.
Abstract:
Several organoselenium compounds have been shown to have powerful anticarcinogenic activity. In view of certain similarities between selenium and sulfur biochemistry, we have evaluated the chemopreventive efficacy of three pairs of analogs using the 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor model in rats. The compounds tested were selenocystamine/cysteamine, Semethylselenocysteine/S-methylcysteine, selenobetaine/sulfobetaine. In the first study, each agent was added to the basal AIN-76A diet and was given before and continued after DMBA treatment until the end. All three selenium compounds were active; a 50% inhibition was achieved at approximately 25 x 10(-6) mol/kg with Se-methylselenocysteine and selenobetaine and at approximately 40 x 10(-6) mol/kg with selenocystamine. In the sulfur series, only cysteamine and S-methylcysteine produced anticancer activity, and the levels required for comparable responses were 500- to 750-fold higher compared to the corresponding selenium analogs. Sulfobetaine was inactive even when present at near maximally tolerated levels. In the second study, Se-methylselenocysteine and S-methylcysteine were chosen for further examination during the initiation and post-initiation phases of mammary carcinogenesis. Se-Methylselenocysteine was effective when it was given either before or after DMBA administration. In contrast, S-methylcysteine was effective only after DMBA treatment. Thus, compared to the sulfur structural analogs, selenium compounds are much more active in cancer protection and may have a multi-modal mechanism in preventing cellular transformation as well as in delaying or inhibiting the expression of malignancy after carcinogen exposure.
Insights
Organoselenium compounds show potent cancer prevention, significantly outperforming sulfur analogs in a rat mammary tumor model. Selenium
Area of Science:
- Biochemistry
- Oncology
- Nutritional Science
Background:
- Organoselenium compounds exhibit promising anticarcinogenic properties.
- Similarities between selenium and sulfur biochemistry warrant comparative studies.
- The 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumor model in rats is a standard for evaluating chemopreventive agents.
Purpose of the Study:
- To evaluate the chemopreventive efficacy of selenium and sulfur analogs in a rat mammary tumor model.
- To compare the potency of organoselenium compounds versus their sulfur counterparts.
- To investigate the optimal timing for administration of chemopreventive agents during carcinogenesis.
Main Methods:
- Three pairs of selenium/sulfur analogs (selenocystamine/cysteamine, Se-methylselenocysteine/S-methylcysteine, selenobetaine/sulfobetaine) were tested.
- Compounds were administered orally via diet before and after DMBA treatment.
- Dose-response relationships and efficacy during initiation and post-initiation phases were assessed.
Main Results:
- All three tested selenium compounds demonstrated significant anticancer activity.
- Selenium compounds achieved 50% tumor inhibition at much lower doses (25-40 x 10^-6 mol/kg) compared to sulfur analogs (500-750 fold higher).
- Se-methylselenocysteine showed efficacy regardless of administration timing relative to DMBA, while S-methylcysteine was effective only post-DMBA.
Conclusions:
- Organoselenium compounds are significantly more potent chemopreventive agents than their sulfur analogs.
- Selenium compounds may act through multiple mechanisms to prevent cancer initiation and progression.
- These findings highlight the therapeutic potential of organoselenium compounds in cancer chemoprevention.