Se-enriched vegetables and cancer reductionSe-enriched vegetables and cancer reduction

P. D. WHANGER, PhD.P. D. WHANGER, PhD.Department of Environmental & Department of Environmental &

Molecular ToxicologyMolecular Toxicology

Oregon State UniversityOregon State UniversityCorvallis, OR. 97330Corvallis, OR. 97330

Low

Variable

Adequate

Accumulators

SELENIUM LEVELS

Shamberger and Frost Can. Med. Assoc. J. 104:82 (1969)—reported inverse relationship of selenium intake with cancer

Shamberger and WillisCRC Crit. Rev. Clin. Lab. Sci. 2: 211 (1971)—more detailed study showing this same inverse relationship

Schrauzer et alBioinorganic Chem. 7:23 (1977)--27-country comparison revealed certain cancers varied inversely with estimated per capita selenium intake

Epidemiological StudiesEpidemiological Studies

Selenium and Tumors with Small AnimalsSelenium and Tumors with Small Animals

There have been over 100 experiments conducted (Combs and Gray, Pharmacol. Ther. 79: 179 (1998)

(a)Two-thirds of animal studies showedstatistically significant reductions of tumors by selenium

(b)One-half showed reductions of 50% or more by selenium

Modified From J. Amer. Med. Assoc. 276: 1957 (1996)Modified From J. Amer. Med. Assoc. 276: 1957 (1996)

Effects of Selenium on Cancer in HumansEffects of Selenium on Cancer in Humans

H2Se

Proteins

Selenocysteine

SeO4

GSSeH

GSSeSG

SeO3

ATP

Se-adenosylselenomethionine

Selenomethionine

Selenohomocysteine

Selenocystathionine

Succinyl homocysteine

Acetate

Acetylserine

-keto--methyl selenobutyrate

Se-methylselenocysteine

glutamine

dimethylselenopropionate

GSH

ATP

adenosine

Se-adenosylselenocysteine

Se-methylselenomethionine

-glutamyl –Se methyl Selenocysteine

-glutamyl Selenocystathionine

GSSG

ADP

ADP

Succinate

Se-methylSeCysSe-oxide

Dimethyldiselenide

dimethyl selenide

(CH3)3Se+

(CH3)2Se

CH3SeH

H2Se

GS-Se-SG

GS-SeH

SeO3

SeO4

selenophosphate

Selenoproteins(as selenocysteine)

selenocysteine

selenomethionine

General body proteins

-glutamyl-Se-methyl selenocysteine

Se-methyl selenocysteine

methyl seleno propionate

-keto--methyl selenobutyrate

selenocystathionine

Anticarcinogenic Efficacy of Different Selenium CompoundsAnticarcinogenic Efficacy of Different Selenium Compounds for Reduction of Mammary Tumors in Ratsfor Reduction of Mammary Tumors in Rats

Nutr. Cancer 17:279 (1992)Nutr. Cancer 17:279 (1992)

Mammary Tumors in Rats Fed Various DietsMammary Tumors in Rats Fed Various Diets

Effect of Selenium on the Incidence of Tumors in RatsEffect of Selenium on the Incidence of Tumors in Rats Injected with MethylnitrosoureaInjected with Methylnitrosourea

Mammary Cancer Prevention in Rats Fed Different Mammary Cancer Prevention in Rats Fed Different Sources of SeleniumSources of Selenium

Effect of Dietary Form of Selenium on Tissue Selenium Effect of Dietary Form of Selenium on Tissue Selenium Concentrations in RatsConcentrations in Rats

JJ. Agric Food Chem. 49: 2681 (2001). Agric Food Chem. 49: 2681 (2001)

CarcinogenesisCarcinogenesis 15: 573 (1994) 15: 573 (1994)

Tissue Selenium Levels in Rats Fed Different Tissue Selenium Levels in Rats Fed Different Sources of SeleniumSources of Selenium

Mammary cancer prevention by selenium enriched garlic orMammary cancer prevention by selenium enriched garlic orselenium enriched yeast in the DMBA and MNU modelsselenium enriched yeast in the DMBA and MNU models

Percent Composition of Identified Selenium Species Percent Composition of Identified Selenium Species of Selenized Garlic and Yeastof Selenized Garlic and Yeast

J. Agric Chemistry, 48:2065 (2000)J. Agric Chemistry, 48:2065 (2000)

J. Agric. Food Chem., Vol: 48, No. 6, 2000

Figure 6. Structures of -glutamyl-Se-methylselenocysteine, Se-methylselenocysteine, and selenomethionine.

NH-CO-CH2-CH2-CH(NH2)-COOH |CH3-Se-CH2-CH-COOH

(-glutamyl-Se-methylselenocysteine)

CH3-Se-CH2-CH(NH2)-COOH

(Se-methylselenocysteine)

CH3-Se-CH2-CH2-CH(NH2)-COOH

(Selenomethionine)

Percentages of Total Selenium as SeMCYS Percentages of Total Selenium as SeMCYS in Selenium Enriched Plantsin Selenium Enriched Plants

Summarized in J. American College of Nutrition 21: 223 (2002)Summarized in J. American College of Nutrition 21: 223 (2002)

Ramps

Garlic

Onions

Broccoli florets

Broccoli sprouts

35-60

47-87

42-55

63

45

Plants% Se as SeMCYS

Effect of Dietary Form of Selenium on Total Number Effect of Dietary Form of Selenium on Total Number of Aberrant Crypt Foci in Ratsof Aberrant Crypt Foci in Rats

JJ. Agric Food Chem. 49: 2681 (2001). Agric Food Chem. 49: 2681 (2001)

Effect of Dietary Form and Amount of Selenium on Colon Tumors in RatsEffect of Dietary Form and Amount of Selenium on Colon Tumors in Rats

JJ. Nutr. 130:2384 (2000). Nutr. 130:2384 (2000)

Wheat and Broccoli

• High Selenium wheat reduced colon tumors in rats but selenomethionine was not very effective in this reduction. Biofactors 14: 191 (2001).

• High selenium broccoli reduced colon tumors in rats, but will SEMCYS be effective (Finley, personal communication)

• SELENOMETHIONINESELENOMETHIONINE- Primary form of Se in enriched yeast, wheat, corn, rice and

soybeans

• Se-METHYLSELENOCYSTEINESe-METHYLSELENOCYSTEINE- Primary form of Se in Astragalus, enriched garlic, broccoli (florets and sprouts), onions and ramps

300

400

200

100

0

Addition to soil Sprayed on Leaves

Se

in b

rocc

oli

µg

/gm

Uptake of Selenium from Soil versus LeavesUptake of Selenium from Soil versus Leaves

Effects of Sticker on the Uptake of Selenium by BroccoliEffects of Sticker on the Uptake of Selenium by Broccoli

Selenium Uptake by Broccoli Sprouts

0

100

200

300

0 10 20 30

Se concentration in water (µg/ml)

Se

co

nc

. in

Sp

rou

ts (

µg

/g)

ConclusionsConclusions

1. Selenium enriched garlic, broccoli florets, onions and ramps significantly reduced mammary tumors in rats.

2. Selenium enriched broccoli (florets and sprouts) and wheat reduced colon tumors in rats.

3. These selenium enriched vegetables did not result in excessive tissue accumulation of selenium and thus are safe for human consumption.

4. SeMCYS is the most effective selenocompound in plants for reduction of mammary tumors in rats. Methylselenol appears to be the specific selenocompound that is effective against mammary tumors.

Accumulation of Selenium inblood, kidney, and liver fromrats fed a selenium-enriched diet

Accumulation of Selenium inmuscle and testes from ratsfed a selenium-enriched diet

Control SEL SeM SeR SeR+SeM

Control = basal diet SEL = selenate SeM = selenomethionine SeR = Se-enriched ramps

Schematic flow chart showing the main sites where selenobetaine,Se-methyselenocysteine, selenobetaine methyl ester, and dimethyl-selenoxide enter the selenium metabolic pathway.

Selenium in Biology and Human Health, p 173, Springer Verlag, New YorkSelenium in Biology and Human Health, p 173, Springer Verlag, New York

Wheat and Broccoli

• High selenium wheat reduced colon tumors

Acknowledgment

My collegues: C. Ip (Roswell Park Cancer Institute, Buffalo, NY; C. Polan and G. Welbaum, Virginia

Technical University; and P. Uden, University of Massachusetts.

Acknowledgment

• We are grateful to Judy Butler and Yu Sun for doing the selenium analyses and the bioavailability study

• Thanks to R. Hafez and M. Kotrebai for the selenium speciation.

• Thanks to Wendy Werks, John Chandler; Johnny, Ruby, Harvey and Debbie Whanger; Jeannie, Keith, Zemry and Margaret Lou Crookshanks; Wayne and Beverly Hinkle; and Bill Definbaugh who worked on various aspects of this project.