The Journal of Simplified Cancer Research (JSCR) - New Article Release
Sulforaphane - its chemistry and anti-cancer properties
Are cruciferous vegetables cancer fighters and cancer preventive?
By Ayguen Sahin, MSc, PhD | Cancer Education and Research Institute (CERI) - CEO, Founder, and Cancer Lead
More details of this article can be found in our JSCR Journal - Issue September 2016
More details of this article can be found in our JSCR Journal - Issue September 2016

Consumption of vegetables, especially cruciferous vegetables, reduces the risk of developing cancer (1). Although the mechanisms of this protection were unclear in the 1990’ies, now more and more in vitro (cell culture) and in vivo (animal models) research provides us with much more clarity on the molecular mechanisms of the anti-cancer and anti-obesity effects of cruciferous vegetables. Molecular mechanisms of the effects of crucifers have further been dissected for heart diseases and autism. Here we have compiled detailed information on Sulforaphane, a molecule isolated from cruciferous vegetables, including the latest research on its health benefits.
What is Sulforaphane?
Sulforaphane is a phytochemical (a molecule naturally found in plants) compound, which belongs to the isothiocyanates family. Sulforaphane is bound to a sugar molecule, called sulforaphane glucosinolate.
Where does Sulforaphane occur?
The compound Sulforaphane glucosinolate is found in cruciferous vegetables. These vegetables include cauliflower, cabbage, garden cress, bok choy, broccoli, and brussels sprouts (see image below) (2).
Sulforaphane is released only after physically breaking the plant, such as eating, chewing, or puréeing. Upon damage to the vegetable, the enzyme (a biological molecule that catalyzes – or accelerates – chemical reactions in the body) myrosinase transforms Glucoraphanin into Sulforaphane (see image below) (3). The richest sources of sulforaphane are young broccoli sprouts and cauliflower.
Sulforaphane is a phytochemical (a molecule naturally found in plants) compound, which belongs to the isothiocyanates family. Sulforaphane is bound to a sugar molecule, called sulforaphane glucosinolate.
Where does Sulforaphane occur?
The compound Sulforaphane glucosinolate is found in cruciferous vegetables. These vegetables include cauliflower, cabbage, garden cress, bok choy, broccoli, and brussels sprouts (see image below) (2).
Sulforaphane is released only after physically breaking the plant, such as eating, chewing, or puréeing. Upon damage to the vegetable, the enzyme (a biological molecule that catalyzes – or accelerates – chemical reactions in the body) myrosinase transforms Glucoraphanin into Sulforaphane (see image below) (3). The richest sources of sulforaphane are young broccoli sprouts and cauliflower.
Sulforaphane and anti-cancer properties
The anti-cancer properties of sulforaphane have been extensively studied in cancer cell lines and animal tumor models. As of today, September 13, 2016, there are 719 research studies published in peer-reviewed journals that studied the potential anti-cancer properties of sulforaphane. The cancer types that have been studied include colon, prostate, breast, lung (non-small cell lung cancer), liver (hepatocellular carcinoma), pancreatic, oral, stomach, bladder cancers, and leukemia.
Many studies have supported the protective effects of broccoli and broccoli sprouts, a high source of suforaphane, against cancer. A recent study from 2016 found that sulforaphane treatment inhibits cell growth (proliferation) and induces cell death (apoptosis) in colon cancer cells while exhibiting negligible toxicity toward normal (nonmalignant) colon cells. These observations were further extended into inhibitory effects against colon tumor growth in an animal model (4).
Sulforaphane can function by blocking the tumor initiation step via inhibiting enzymes (the Phase I enzymes) that convert pro-carcinogens to carcinogens. Sulforaphane also induces other sets of enzymes (the Phase II enzymes), selectively inducing Phase II enzymes without the induction of Phase I enzymes (1), detoxifying carcinogens and facilitating their elimination from the body. Upon tumor initiation, sulforaphane can act via several molecular mechanisms that regulate proliferation (cell growth and expansion) and apoptosis (cell death) signals to suppress cancer progression (5).
A recent study published in the journal International Journal of Oncology in 2015, showed that sulforaphane inhibits human colon cancer progression and cancer cell angiogenesis by inhibiting the hypoxia inducible factor-1α (HIF-1α or HIF-1a, see below) and the hypoxia-induced vascular endothelial growth factor (VEGF, see below) expression (6).
In 2006, a study from the Medical University of South Carolina showed that sulforaphane activates apoptosis in glioblastoma (GBM) cells (7). Yet another recent study published in 2012, showed that sulforaphane inhibited cell proliferation and activated apoptosis of GBM cells (8).
Recent research into the effects of sulforaphane on cancer stem cells (CSCs) has drawn lots of interest. CSCs are suggested to be responsible for initiating and maintaining cancer and contributing to recurrence and drug resistance. Many studies have indicated that sulforaphane may target CSCs in different types of cancer through modulation of NF-κB, SHH, epithelial-mesenchymal transition, and Wnt/β-catenin pathways. (reviewed in 9)
A study published in 2010 in the journal Clinical Cancer Research showed that sulforaphane inhibits breast CSCs and downregulates the Wnt/beta-catenin self-renewal pathway. (10)
A study, published in 2002 in the journal PNAS, showed that sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo-a-pyrene-induced stomach tumors (11)
Another important point is to mention that combination therapy with sulforaphane and chemotherapy in preclinical settings has shown promising results. (9)
The anti-cancer properties of sulforaphane have been extensively studied in cancer cell lines and animal tumor models. As of today, September 13, 2016, there are 719 research studies published in peer-reviewed journals that studied the potential anti-cancer properties of sulforaphane. The cancer types that have been studied include colon, prostate, breast, lung (non-small cell lung cancer), liver (hepatocellular carcinoma), pancreatic, oral, stomach, bladder cancers, and leukemia.
Many studies have supported the protective effects of broccoli and broccoli sprouts, a high source of suforaphane, against cancer. A recent study from 2016 found that sulforaphane treatment inhibits cell growth (proliferation) and induces cell death (apoptosis) in colon cancer cells while exhibiting negligible toxicity toward normal (nonmalignant) colon cells. These observations were further extended into inhibitory effects against colon tumor growth in an animal model (4).
Sulforaphane can function by blocking the tumor initiation step via inhibiting enzymes (the Phase I enzymes) that convert pro-carcinogens to carcinogens. Sulforaphane also induces other sets of enzymes (the Phase II enzymes), selectively inducing Phase II enzymes without the induction of Phase I enzymes (1), detoxifying carcinogens and facilitating their elimination from the body. Upon tumor initiation, sulforaphane can act via several molecular mechanisms that regulate proliferation (cell growth and expansion) and apoptosis (cell death) signals to suppress cancer progression (5).
A recent study published in the journal International Journal of Oncology in 2015, showed that sulforaphane inhibits human colon cancer progression and cancer cell angiogenesis by inhibiting the hypoxia inducible factor-1α (HIF-1α or HIF-1a, see below) and the hypoxia-induced vascular endothelial growth factor (VEGF, see below) expression (6).
In 2006, a study from the Medical University of South Carolina showed that sulforaphane activates apoptosis in glioblastoma (GBM) cells (7). Yet another recent study published in 2012, showed that sulforaphane inhibited cell proliferation and activated apoptosis of GBM cells (8).
Recent research into the effects of sulforaphane on cancer stem cells (CSCs) has drawn lots of interest. CSCs are suggested to be responsible for initiating and maintaining cancer and contributing to recurrence and drug resistance. Many studies have indicated that sulforaphane may target CSCs in different types of cancer through modulation of NF-κB, SHH, epithelial-mesenchymal transition, and Wnt/β-catenin pathways. (reviewed in 9)
A study published in 2010 in the journal Clinical Cancer Research showed that sulforaphane inhibits breast CSCs and downregulates the Wnt/beta-catenin self-renewal pathway. (10)
A study, published in 2002 in the journal PNAS, showed that sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo-a-pyrene-induced stomach tumors (11)
Another important point is to mention that combination therapy with sulforaphane and chemotherapy in preclinical settings has shown promising results. (9)
Cruciferous vegetables and the immune system
Cruciferous vegetables do much more than provide anti-cancer properties and protect against cancer. Both broccoli and cauliflower are also packed with vitamin C and vitamin B folate as well as vitamin A (broccoli), which all are important to boost the immune system (12, 13, 14).
Sulforaphane and other health benefits
Heart health, diabetes, obesity, and autism
Sulforaphane is not only important for cancer cell elimination and cancer prevention, but also has other health benefits: it helps prevent diabetic cardiomypathy (a disorder of heart muscle in diabetic people) (15) and helps protect against ischemic injury of the heart through an antioxidant pathway (16).
In a recent study, sulforaphane has been found to improve insulin responsiveness in a diabetic animal model (17). In another recent study, sulforaphane decreased obesity by inhibiting adipogenesis [a process by which fat cells differentiate from pre-adipocytes to adipocytes (fat cells)] in an obese animal model (18). In a recent study from Harvard Medical School, Massachusetts General Hospital, published in 2014 in the journal PNAS, sulforaphane, derived from broccoli sprouts, showed substantial declines in symptoms (improvement of behavior) of Autism Spectrum Disorder (ASD) patients compared to the placebo group (19).
How to eat cruciferous vegetables for higher sulforaphane concentrations?
A recent study published in 2016 in the Journal of Food Chemistry demonstrated that sulforaphane concentrations were up to 10 times higher in raw and 1 min steamed broccoli samples after digestion (remember, we must physically break, e.g. chew the cruciferous vegetables to get the most sulforaphane) compared to longer-steamed broccoli. The study further showed that protein or lipid addition had no influence on the formation and bioaccessibility of sulforaphane. (3)
Cruciferous vegetables do much more than provide anti-cancer properties and protect against cancer. Both broccoli and cauliflower are also packed with vitamin C and vitamin B folate as well as vitamin A (broccoli), which all are important to boost the immune system (12, 13, 14).
Sulforaphane and other health benefits
Heart health, diabetes, obesity, and autism
Sulforaphane is not only important for cancer cell elimination and cancer prevention, but also has other health benefits: it helps prevent diabetic cardiomypathy (a disorder of heart muscle in diabetic people) (15) and helps protect against ischemic injury of the heart through an antioxidant pathway (16).
In a recent study, sulforaphane has been found to improve insulin responsiveness in a diabetic animal model (17). In another recent study, sulforaphane decreased obesity by inhibiting adipogenesis [a process by which fat cells differentiate from pre-adipocytes to adipocytes (fat cells)] in an obese animal model (18). In a recent study from Harvard Medical School, Massachusetts General Hospital, published in 2014 in the journal PNAS, sulforaphane, derived from broccoli sprouts, showed substantial declines in symptoms (improvement of behavior) of Autism Spectrum Disorder (ASD) patients compared to the placebo group (19).
How to eat cruciferous vegetables for higher sulforaphane concentrations?
A recent study published in 2016 in the Journal of Food Chemistry demonstrated that sulforaphane concentrations were up to 10 times higher in raw and 1 min steamed broccoli samples after digestion (remember, we must physically break, e.g. chew the cruciferous vegetables to get the most sulforaphane) compared to longer-steamed broccoli. The study further showed that protein or lipid addition had no influence on the formation and bioaccessibility of sulforaphane. (3)
References:
1. Zhang Y et al., A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2399-403.
2. Phytochemicals http://www.phytochemicals.info/phytochemicals/sulforaphane.php Accessed on September 13, 2016
3. Sarvan I et al., Sulforaphane formation and bioaccessibility are more affected by steaming time than meal composition during in vitro digestion of broccoli. Food Chem. 2017 Jan 1;214:580-6. Epub 2016 Jul 19.
4. Byun S. et al. Sulforaphene suppresses growth of colon cancer-derived tumors via induction of glutathione depletion and microtubule depolymerization. Mol Nutr Food Res. 2016 May;60(5):1068-78.
5. American Nutrition Association http://americannutritionassociation.org/newsletter/cancer-fighting-foods Accessed on Sept 13, 2016
6. Kim DH et al., Sulforaphane inhibits hypoxia-induced HIF-1α and VEGF expression and migration of human colon cancer cells. Int J Oncol. 2015 Dec;47(6):2226-32.
7. Karmakar S et al., Activation of multiple molecular mechanisms for apoptosis in human malignant glioblastoma T98G and U87MG cells treated with sulforaphane. Neuroscience. 2006 Sep 1;141(3):1265-80.
8. Huang TY et al., Effect of sulforaphane on growth inhibition in human brain malignant glioma GBM 8401 cells by means of mitochondrial- and MEK/ERK-mediated apoptosis pathway. Cell Biochem Biophys. 2012 Jul;63(3):247-59.
9. Li Y, and Zhang T. Targeting cancer stem cells with sulforaphane, a dietary component from broccoli and broccoli sprouts. Future Oncol. 2013 Aug;9(8):1097-103.
10. Li Y et al., Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin Cancer Res. 2010 May 1;16(9):2580-90.
11. Fahey, JW et al., Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo-a-pyrene-induced stomach tumors. PNAS, May 28, 2002;99(11):7610-7615
12. Overview of the Immune System. http://lpi.oregonstate.edu/mic/micronutrients-health/immunity Accessed on September 14, 2016
13. USDA Food Composition Databases. https://ndb.nal.usda.gov/ndb Accessed on September 14, 2016
14. Cancer Education and Research Institute, Educational Info Grafic (German), Broccoli.
15. Bai Y et al., Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation. J Mol Cell Cardiol. 2013 Apr;57:82-95.
16. Piao CS et al., Sulforaphane protects ischemic injury of hearts through antioxidant pathway and mitochondrial K(ATP) channels.
Pharmacol Res. 2010 Apr;61(4):342-8.
17. de Souza CG et al., Sulforaphane ameliorates the insulin responsiveness and the lipid profile but does not alter the antioxidant response in diabetic rats. Food Funct. 2016 Apr;7(4):2060-5.
18. Choi KM et al., Sulforaphane attenuates obesity by inhibiting adipogenesis and activating the AMPK pathway in obese mice. J Nutr Biochem. 2014 Feb; 25(2):201-7.
19. Singh K et al., Sulforaphane treatment of autism spectrum disorder (ASD) Proc Natl Acad Sci U S A. 2014 Oct 28; 111(43): 15550–15555.
1. Zhang Y et al., A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2399-403.
2. Phytochemicals http://www.phytochemicals.info/phytochemicals/sulforaphane.php Accessed on September 13, 2016
3. Sarvan I et al., Sulforaphane formation and bioaccessibility are more affected by steaming time than meal composition during in vitro digestion of broccoli. Food Chem. 2017 Jan 1;214:580-6. Epub 2016 Jul 19.
4. Byun S. et al. Sulforaphene suppresses growth of colon cancer-derived tumors via induction of glutathione depletion and microtubule depolymerization. Mol Nutr Food Res. 2016 May;60(5):1068-78.
5. American Nutrition Association http://americannutritionassociation.org/newsletter/cancer-fighting-foods Accessed on Sept 13, 2016
6. Kim DH et al., Sulforaphane inhibits hypoxia-induced HIF-1α and VEGF expression and migration of human colon cancer cells. Int J Oncol. 2015 Dec;47(6):2226-32.
7. Karmakar S et al., Activation of multiple molecular mechanisms for apoptosis in human malignant glioblastoma T98G and U87MG cells treated with sulforaphane. Neuroscience. 2006 Sep 1;141(3):1265-80.
8. Huang TY et al., Effect of sulforaphane on growth inhibition in human brain malignant glioma GBM 8401 cells by means of mitochondrial- and MEK/ERK-mediated apoptosis pathway. Cell Biochem Biophys. 2012 Jul;63(3):247-59.
9. Li Y, and Zhang T. Targeting cancer stem cells with sulforaphane, a dietary component from broccoli and broccoli sprouts. Future Oncol. 2013 Aug;9(8):1097-103.
10. Li Y et al., Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells. Clin Cancer Res. 2010 May 1;16(9):2580-90.
11. Fahey, JW et al., Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo-a-pyrene-induced stomach tumors. PNAS, May 28, 2002;99(11):7610-7615
12. Overview of the Immune System. http://lpi.oregonstate.edu/mic/micronutrients-health/immunity Accessed on September 14, 2016
13. USDA Food Composition Databases. https://ndb.nal.usda.gov/ndb Accessed on September 14, 2016
14. Cancer Education and Research Institute, Educational Info Grafic (German), Broccoli.
15. Bai Y et al., Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation. J Mol Cell Cardiol. 2013 Apr;57:82-95.
16. Piao CS et al., Sulforaphane protects ischemic injury of hearts through antioxidant pathway and mitochondrial K(ATP) channels.
Pharmacol Res. 2010 Apr;61(4):342-8.
17. de Souza CG et al., Sulforaphane ameliorates the insulin responsiveness and the lipid profile but does not alter the antioxidant response in diabetic rats. Food Funct. 2016 Apr;7(4):2060-5.
18. Choi KM et al., Sulforaphane attenuates obesity by inhibiting adipogenesis and activating the AMPK pathway in obese mice. J Nutr Biochem. 2014 Feb; 25(2):201-7.
19. Singh K et al., Sulforaphane treatment of autism spectrum disorder (ASD) Proc Natl Acad Sci U S A. 2014 Oct 28; 111(43): 15550–15555.
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