Life Extension Magazine®
Heads of broccoli with robust amounts of absorbable sulforaphane

The Anti-Cancer Effects of Broccoli

In 1992, researchers at Johns Hopkins discovered robust anti-cancer properties of a broccoli compound called sulforaphane. Thirty years later oncologists remain in the dark about this plant compound. A unique delivery system enables higher levels of sulforaphane to enter the bloodstream.

By William Faloon.

William Faloon
William Faloon

In 1992, researchers at Johns Hopkins discovered robust anti-cancer properties of a broccoli compound called sulforaphane.1

One study demonstrated a 61% reduction in tumor incidence in lab rats given high-potency sulforaphane compared to controls.2

The media reported on these findings and predicted sulforaphane would soon become available to prevent and help treat certain malignancies.3

Here we are nearly 30 years later, and conventional oncology remains in the dark about this natural plant compound. Few understand what is needed for sulforaphane to be absorbed into their bloodstream.

What has not stopped is an avalanche of scientific studies showing greater anti-cancer effects than originally anticipated.

When seeking better ways to prevent and treat head and neck cancers, I searched the National Library of Medicine’s website (www.Pubmed.gov).

I was astounded to see the volume of published research about sulforaphane’s potential ability to reduce risks of many different cancers.

The box on this page shows the surging number of studies between 1992 and 2021 on the federal government’s website that discuss “broccoli and cancer.4

I succinctly describe some of these findings in this editorial.

Published Studies Discussing Broccoli and Cancer 1992-mid-2021

Bar chart showing number of published studies by year

The National Library of Medicine provides free access to its massive data base of scientific papers (www.Pubmed.gov). This graph shows the surging number of published studies that discus “broccoli and cancer” as of mid-2021.

There may be no greater a defining moment in one’s life than a cancer diagnosis.

All kinds of treatment choices are available, usually toxic in the near and long term, with no guarantee of a complete response.

Upon diagnosis, a patient often forfeits their personal freedoms in order to be treatment compliant.

In essence, the cancer and rigorous therapies control every aspect of the patient’s schedule, along with taking a relentless toll on their physical, financial, and emotional wellbeing.

Proven strategies exist to lower one’s risk of developing a malignancy. Yet these methods are disregarded by most of the world’s population.5-7

Dietary intake of cruciferous vegetables like broccoli and cauliflower have demonstrated cancer risk reductions.8-10

Compelling studies reveal that sulforaphane may be the most potent anti-cancer compound in these vegetables.1,11,12

Additional research findings describe how people can deliver high levels of sulforaphane to cells throughout their body.

What Makes Cancer Cells Treatment Resistant?

Woman scientiest studying cancer cells and their resistance

Cancer cells are everything we would like our healthy cells to be.

They quickly adapt to toxic environments (such as chemo drugs), they readily alter themselves to assure continued survival, and they utilize genetic mechanisms to promote cellular immortality.

All of these factors make cancer difficult to treat.

Sulforaphane long ago demonstrated cancer preventive properties in cell culture and in mammals via multiple mechanisms.

Recent studies suggest that sulforaphane favorably regulates key genes that influence the initiation and progression of cancer. These data led to a study published in 2018 that concluded:13

“This research may provide a basis for the clinical use of sulforaphane for cancer chemoprevention and enable us to design preventive strategies for cancer management, reduce cancer development and recurrence, and thus improve patient survival.”

These data were bolstered by a 2020 report describing how sulforaphane impacts the function of microRNAs by tumor cells.14

MicroRNAs are small stretches of genetic material involved in biological processes that include cell cycle regulation, proliferation, apoptosis, and differentiation.14

Impairment in the expression and function of microRNAs has been associated with cancer risk.14

Sulforaphane beneficially regulates microRNAs in ways that interfere with survival mechanisms used by cancer cells to escape eradication.14

Head and Neck Cancer Outbreak

Incidence of head and neck cancer has increased 300% in men over the last two decades.15,16

Tobacco used to be the main culprit, but a major underlying cause today is infection with the human papilloma virus (HPV).17-19

Some encouraging news for non-smokers is that HPV-induced head and neck cancers respond much better to conventional treatments. These treatments, however, are often harsh, and radiation-inflicted pain can persist for months.

A study conducted in Taiwan adjusted for common risk factors (alcohol/tobacco) and found the following associations between head and neck cancer risk and intake of fruit and vegetables:20

  • Daily intake of vegetables: 56% risk reduction
  • Daily intake of fruit: 45% risk reduction

Individuals with no intake of fruit and vegetables had more than double the risk of head and neck cancer compared to daily fruit/vegetable intake.

This study is consistent with others showing protective effects in response to higher ingestion of plant foods.21-24

One study found those who smoke cigarettes and eat processed meats had nearly triple the risk of head and neck cancer. This same study observed decreases in head and neck cancers in response to higher fruit and vegetable intake.25

HPV infection adds yet another risk factor for head and neck cancer.

In fact, in many developed countries, HPV is by far the most important risk factor for primary oropharyngeal squamous cell carcinoma, even exceeding smoking and alcohol.26

Evidence Supporting Preventative Role of Sulforaphane

Man having scan of head being preformed

Chronic exposure to carcinogens (such as tobacco) is a risk factor for head and neck malignancies.

A group of researchers initially examined the impact of sulforaphane on normal mucosal cells and head and neck cancer cell lines.27

They went further and performed a study on a mouse model of oral cancer. This was followed by a pilot trial on 10 healthy volunteers, to investigate bioavailability and pharmacodynamic properties of three different broccoli-sprout preparations.

In the cell-line portion of the study, researchers demonstrated that treatment of both normal and head and neck cancer cells with sulforaphane turned on genes involved in the detoxification of known carcinogens.

Compared to controls, ingestion of sulforaphane significantly reduced the incidence and size of toxin-induced tongue tumors in mice.

When humans were administered different broccoli-sprout preparations, in up to 66% of the study subjects, there was a 2-fold or greater upregulation of a gene involved in detoxification reactions.27

Enhancing Cell-Killing Impact of Conventional Therapy

Radiation therapy is debilitating, but it enables significant numbers of head and neck cancer patients to achieve complete responses and outright cures.

A cell culture study found that when sulforaphane was combined with radiation (cancer cells were pretreated with sulforaphane before being irradiated), there was a stronger inhibition of proliferation and survival of head and neck cancer cells.28 The authors of this study concluded that sulforaphane is a promising agent in the treatment of head and neck cancer due to its antiproliferative and radio-sensitizing properties.

My complaint here is, it was published in 2011 and I’ve yet to hear of a radiation oncologist advising head and neck cancer patients to fortify their diet with sulforaphane-precursor foods or supplements.

Photodynamic therapy is another method to treat cancers using photosensitizers and light. It is particularly effective in early-stage oral cancers.29

The clinical application of this therapy is limited by the toxicity of the photosensitizer and narrow therapeutic effects against fully developed malignancies.

A study measured the effect of photodynamic therapy combined with sulforaphane on human head and neck cancer cells.

Pre-treating cancer cells with sulforaphane before photodynamic therapy significantly decreased cellular viability and increased apoptosis (cell death) in these human head and neck cancer cell lines.29

This study was published in 2015. I have yet to hear of an oncologist advising photodynamic-treated patients to increase their intake of sulforaphane precursors.

Attacking Cancer Stem Cells

Example of thyroid cancer and it's cells

Healthy stem cells perform essential regenerative functions throughout one’s body.

Cancer stem cells, on the other hand, give rise to malignant cells that then propagate on their own. Cancer stem cells are highly resistant to conventional treatments and are an origin of tumor metastasis.30

While conventional therapies readily kill offspring malignant cells, surviving cancer stem cells produce new cells that are often treatment resistant. It’s a major reason why even pancreatic cancers initially regress in response to chemotherapy, but then come raging back virtually invulnerable to further toxic treatments.31

A study published in 2020 tested sulforaphane in combination with chemotherapy drugs against human head and neck cancer stem cells.32

The study found that sulforaphane reduced viability of the cancer stem cells in a time- and dose-dependent manner.

Combining sulforaphane with the chemo drug cisplatin increased cancer stem cell cytotoxicity by 2-fold and by 10-foldwhen combined with the chemo drug 5-fluorouracil, compared to sulforaphane alone. There was no toxicity to non-cancerous stem cell function and viability.32

The conclusion of this study was that combining sulforaphane with lower doses of the toxic chemo drugs might enhance cytotoxicity against human head and neck cancer stem cells.

Cancer stem cells are driving forces in head and neck cancers of the oral cavity.33

A study published in 2017 looked at the effect of sulforaphane on oral cancer stem cells. Sulforaphane treatment of these cancer stem cells decreased the migration, invasion, clonogenicity, and in vivo tumor formation when these cells were grafted into whole animals.33

The scientists attributed some of the benefits of sulforaphane treatment to a dose-dependent increase in the levels of a tumor suppressive microRNA.

The authors concluded that these lines of evidence suggest that sulforaphane can suppress cancer stem cell viability and tumor-initiating properties both in vitro and in vivo.

Well-controlled clinical trials on head and neck cancer patients using differing doses of sulforaphane precursors to assess real-world efficacy are lacking.

Sulforaphane Impedes Thyroid Cancer

Thyroid cancer incidence has rapidly increased in recent years37 and is now estimated to be the seventh most common cancer in women.38

A scientific group investigated the therapeutic potential of sulforaphane against thyroid cancer cells and explored the mechanisms underlying its anti-tumor effects.39

The researchers showed that sulforaphane significantly inhibited thyroid cancer cell proliferation in a dose- and time-dependent manner.

They identified specific anti-cancer genes and signaling factors that enable sulforaphane to inhibit invasiveness of thyroid cancer cells.

When thyroid cancer cells were grafted into mice, sulforaphane significantly inhibited tumor growth.

The authors state that theirs is the first study to demonstrate underlying mechanisms that make sulforaphane a potential adjuvant treatment against thyroid cancers. It was published in 2015 but has not yet made an impact on mainstream oncology practice.

Prostate and Tongue Cancers

Fresh vegetables with naturally occurring sulforaphane

Sulforaphane has been shown to induce cancer cell apoptosis (self-destruction), inhibit progression of benign lesions into malignant tumors, and interrupt metastasis.40

Thirteen years ago, a preclinical study found that sulforaphane regulates genes that enable initiation and metastasis of tongue cancer (one of many types of human head and neck cancers).40

The beneficial properties of sulforaphane include inhibiting angiogenesis, the formation of new blood vessels that feed rapidly dividing malignant cells.39

This same study showed the sulforaphane induced these protective effects against a line of prostate cancer cells.40

Head and neck cancers include those of the tongue and are increasing in incidence because of the HPV virus, especially in men.18,19

This study demonstrated in vitro the effectiveness of sulforaphane as a preventive compound against tongue cancers and prostate cell angiogenesis.

More recent epidemiological studies on human populations show markedly reduced cancer incidence in those consuming fresh vegetables.21-24

“Breast Cancer Prevention—Is there a Future for Sulforaphane and Its Analogs?”

The headline in this box is that of a 2020 published review of human studies indicating that vegetables rich in sulforaphane may reduce breast cancer risk.34

This comprehensive report presents data on the beneficial impact of sulforaphane against signaling pathways that initiate and then fuel breast cancer cell propagation and metastasis.34

A paper published in 2019 described how sulforaphane suppressed the growth of triple-negative breast cancer stem cells in vitro and in vivo.35

Triple-negative breast cancers are deadly because they lack typical receptors (estrogen or HER2) that enable effective treatments to be administered.

Estrogen-modulating drugs are effective against estrogen-receptor positive tumors. Herceptin® is used to treat some HER2 receptor cancers.

A 2017 systematic review and meta-analysis found a combination of sulforaphane + epigallocatechin gallate (from green tea) restored estrogen receptor expression in a line of triple-negative breast cancer cells, which would enable estrogen-modulating treatment to be more effectively utilized.36

Despite John Hopkins researchers discovering potent effects of sulforaphane against mammary tumors back in 1992, breast cancer patients today are seldom advised to increase their intake of absorbable oral sulforaphane precursors.

Clinical trials using differing doses and delivery methods of sulforaphane precursors are urgently needed.

Challenge of Obtaining Absorbable Sulforaphane

Including lots of fresh vegetables in one’s diet is of indisputable value.

Mature cruciferous vegetables, however, contain relatively little sulforaphane.

What they provide are varying levels of a sulforaphane precursor called glucoraphanin, which converts to sulforaphane in the gut primarily as a result of the activity of the enzyme myrosinase.

Healthy intestinal enzymes/flora also help in the conversion to sulforaphane in the gut.

Mature broccoli and other cruciferous vegetables lack robust sulforaphane-boosting capacity.

Broccoli sprouts, on the other hand, contain 10 to 100 times more sulforaphane-boosting potential.42

Even so, cooking broccoli or sprouts destroys most of the sulforaphane precursor (glucoraphanin) and the enzyme (myrosinase) needed to convert glucoraphanin (in the intestines) to sulforaphane for absorption into the bloodstream.

Why the Delay?

A comprehensive review of clinical trials investigating broccoli sprouts and other sulforaphane precursors was published in 2021.41

It explains a lot about the ongoing delay in transitioning sulforaphane precursors into routine medical practice. Some highlights from this 2021 report include:

  • Pure sulforaphane was considered a “drug” by the FDA and Institutional Review Boards that approve human research, as recently as the late 1990s or early 2000s. (This meant that stringent clinical trial regulations impeded human research.41)
  • Most of the data regarding mechanisms of action and efficacy were derived from cell culture and animal studies performed with pure sulforaphane.
  • Ascertaining an effective daily dose and dosing schedule requires arduous pilot human studies (adding more years of delay to assess efficacy).
  • Other nutrients contained in cruciferous vegetables (flavonoids, anthocyanins, and carotenoids) might contribute to their anti-cancer properties (even though sulforaphane itself demonstrated remarkable anti-cancer effects in cell culture and animal studies).
  • Huge variations exist in the concentration of sulforaphane precursors (glucoraphanin and myrosinase) in broccoli sprouts depending on species, temperature during growth, light, time to harvest, etc.
  • Presence of food-borne pathogens and other potential contaminants was detected in broccoli spouts.
  • Individual variability of human intestinal flora involved in sulforaphane enzymatic conversion.
  • Lack of standardization of broccoli preparations.

Dietary supplements containing broccoli preparations should be standardized for glucoraphanin and include the enzyme myrosinase to deliver powerful glucoraphane, and be enteric coated to protect against stomach degradation.

This 2021 published review described many diseases beyond cancer for which sulforaphane might be efficacious.

It opened my eyes to the myriad of bureaucratic obstacles that have denied most of the public access to effective sulforaphane-boosting prevention and treatment strategies.

Broccoli sprouts turning into glucoraphanin, myrosinase, then sulforaphane

Swallowing pure sulforaphane is not a solution because it is unstable and mostly degraded in the stomach before reaching the intestines for absorption.

The myrosinase enzyme (found in cruciferous vegetables) is largely destroyed by stomach acid before it can convert glucoraphanin into sulforaphane in the small intestines.

Enteric coated glucoraphanin + myrosinase may be the ultimate solution to these issues.

The chart on the next page shows the pathway of how glucoraphanin (found abundantly in broccoli sprouts) converts to sulforaphane.

Broccoli sprouts contain abundant glucoraphanin that requires the myrosinase enzyme to convert to sulforaphane.

Eating raw broccoli spouts is considered a good dietary way of boosting blood sulforaphane levels.

Some of the challenges of relying on raw broccoli sprouts include:

  • High cost: About $244 a month to obtain decent amounts.
  • Individual variability of gut enzymes: May limit sulforaphane bioavailability.
  • Differing glucoraphanin/myrosinase levels: Even in broccoli sprouts.
  • Inconvenience and taste issues of including broccoli sprouts in daily diet.
  • Bacteria contamination of raw broccoli sprouts: Requires extensive cleansing beyond washing with warm water.
  • High levels of stomach acid can neutralize myrosinase, thus impeding conversion of glucoraphanin to sulforaphane.

In this month’s issue…

Matured broccoli containing les sulforaphane than sprouts

The article on page 60 updates readers on a dual-layered caplet that contains glucoraphanin + myrosinase coated to avoid stomach acid.

This enables sulforaphane to be created in the small intestine , from the reaction of myrosinase and glucoraphanin, and then absorbed into one’s bloodstream.

For me personally, I try to eat broccoli sprouts, but dislike the taste and need for intensive decontamination as bacteria tightly adhere to the surface texture of sprouts.

I include mature cruciferous vegetables in my diet and take a daily standardized glucoraphanin + myrosinase enterically coated tablet.

For those seeking to ingest more healthy foods, the article on page 28 describes a plant-based multivitamin that provides the active nutrients found in three servings of vegetables and two servings of fruit. It’s an efficient way to boost one’s daily intake of these health-promoting foods.

For longer life,

For Longer Life

William Faloon

Life Extension®

References

  1. Zhang Y, Talalay P, Cho CG, 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. Zhang Y, Kensler TW, Cho CG, et al. Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3147-50.
  3. Available at: https://www.baltimoresun.com/news/bs-xpm-1997-09-16-1997259086-story.html. Accessed July 27, 2021.
  4. Available at: https://pubmed.ncbi.nlm.nih.gov/?term=broccoli+and+cancer&filter=years.1992-2021. Accessed July 27, 2021.
  5. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020 Jan;70(1):7-30.
  6. Mentella MC, Scaldaferri F, Ricci C, et al. Cancer and Mediterranean Diet: A Review. Nutrients. 2019 Sep 2;11(9).
  7. Rawla P, Sunkara T, Gaduputi V. Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World J Oncol. 2019 Feb;10(1):10-27.
  8. Verhoeven DT, Goldbohm RA, van Poppel G, et al. Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiol Biomarkers Prev. 1996 Sep;5(9):733-48.
  9. Higdon JV, Delage B, Williams DE, et al. Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis. Pharmacol Res. 2007 Mar;55(3):224-36.
  10. Sturm C, Wagner AE. Brassica-Derived Plant Bioactives as Modulators of Chemopreventive and Inflammatory Signaling Pathways. Int J Mol Sci. 2017 Sep 1;18(9).
  11. Bayat Mokhtari R, Baluch N, Homayouni TS, et al. The role of Sulforaphane in cancer chemoprevention and health benefits: a mini-review. J Cell Commun Signal. 2018 Mar;12(1):91-101.
  12. Tortorella SM, Royce SG, Licciardi PV, et al. Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition. Antioxid Redox Signal. 2015 Jun 1;22(16):1382-424.
  13. Jiang X, Liu Y, Ma L, et al. Chemopreventive activity of sulforaphane. Drug Des Devel Ther. 2018;12:2905-13.
  14. Rafiei H, Ashrafizadeh M, Ahmadi Z. MicroRNAs as novel targets of sulforaphane in cancer therapy: The beginning of a new tale? Phytother Res. 2020 Apr;34(4):721-8.
  15. Available at: https://consumer.healthday.com/sexual-health-information-32/human-papillomavirus-hpv-news-756/1-in-9-american-men-infected-with-oral-hpv-727553.html. Accessed August 4, 2021.
  16. Available at: http://www.chicagotribune.com/lifestyles/health/ct-hpv-oral-cancer-in-men-20180312-story.html. Accessed August 4, 2021.
  17. Maier H, Dietz A, Gewelke U, et al. Tobacco and alcohol and the risk of head and neck cancer. Clin Investig. 1992 Mar-Apr;70(3-4):320-7.
  18. Available at: https://www.cancer.gov/types/head-and-neck/head-neck-fact-sheet. Accessed July 28, 2021.
  19. Rettig E, Kiess AP, Fakhry C. The role of sexual behavior in head and neck cancer: implications for prevention and therapy. Expert Rev Anticancer Ther. 2015 Jan;15(1):35-49.
  20. Chang CC, Lee WT, Lee YC, et al. Investigating the association between diet and risk of head and neck cancer in Taiwan. Oncotarget. 2017 Nov 17;8(58):98865-75.
  21. Riboli E, Norat T. Epidemiologic evidence of the protective effect of fruit and vegetables on cancer risk. Am J Clin Nutr. 2003 Sep;78(3 Suppl):559S-69S.
  22. Farvid MS, Barnett JB, Spence ND. Fruit and vegetable consumption and incident breast cancer: a systematic review and meta-analysis of prospective studies. Br J Cancer. 2021 Jul;125(2):284-98.
  23. Chiao JW, Wu H, Ramaswamy G, et al. Ingestion of an isothiocyanate metabolite from cruciferous vegetables inhibits growth of human prostate cancer cell xenografts by apoptosis and cell cycle arrest. Carcinogenesis. 2004 Aug;25(8):1403-8.
  24. Michnovicz JJ, Adlercreutz H, Bradlow HL. Changes in levels of urinary estrogen metabolites after oral indole-3-carbinol treatment in humans. J Natl Cancer Inst. 1997 May 21;89(10):718-23.
  25. Butler C, Lee YA, Li S, et al. Diet and the risk of head-and-neck cancer among never-smokers and smokers in a Chinese population. Cancer Epidemiol. 2017 Feb;46:20-6.
  26. Economopoulou P, Kotsantis I, Psyrri A. Special Issue about Head and Neck Cancers: HPV Positive Cancers. Int J Mol Sci. 2020 May 11;21(9):3388.
  27. Bauman JE, Zang Y, Sen M, et al. Prevention of Carcinogen-Induced Oral Cancer by Sulforaphane. Cancer Prev Res (Phila). 2016 Jul;9(7):547-57.
  28. Kotowski U, Heiduschka G, Brunner M, et al. Radiosensitization of head and neck cancer cells by the phytochemical agent sulforaphane. Strahlenther Onkol. 2011 Sep;187(9):575-80.
  29. Lee SJ, Hwang HJ, Shin JI, et al. Enhancement of cytotoxic effect on human head and neck cancer cells by combination of photodynamic therapy and sulforaphane. Gen Physiol Biophys. 2015 Jan;34(1):13-21.
  30. Najafi M, Farhood B, Mortezaee K. Cancer stem cells (CSCs) in cancer progression and therapy. J Cell Physiol. 2019 Jun;234(6):8381-95.
  31. Barman S, Fatima I, Singh AB, et al. Pancreatic Cancer and Therapy: Role and Regulation of Cancer Stem Cells. Int J Mol Sci. 2021 Apr 30;22(9).
  32. Elkashty OA, Tran SD. Broccoli extract increases drug-mediated cytotoxicity towards cancer stem cells of head and neck squamous cell carcinoma. Br J Cancer. 2020 Oct;123(9):1395-403.
  33. Liu CM, Peng CY, Liao YW, et al. Sulforaphane targets cancer stemness and tumor initiating properties in oral squamous cell carcinomas via miR-200c induction. J Formos Med Assoc. 2017 Jan;116(1):41-8.
  34. Kuran D, Pogorzelska A, Wiktorska K. Breast Cancer Prevention-Is there a Future for Sulforaphane and Its Analogs? Nutrients. 2020 May 27;12(6).
  35. Castro NP, Rangel MC, Merchant AS, et al. Sulforaphane Suppresses the Growth of Triple-negative Breast Cancer Stem-like Cells In vitro and In vivo. Cancer Prev Res (Phila). 2019 Mar;12(3):147-58.
  36. Gianfredi V, Vannini S, Moretti M, et al. Sulforaphane and Epigallocatechin Gallate Restore Estrogen Receptor Expression by Modulating Epigenetic Events in the Breast Cancer Cell Line MDA-MB-231: A Systematic Review and Meta-Analysis. J Nutrigenet Nutrigenomics. 2017;10(3-4):126-35.
  37. Wiltshire JJ, Drake TM, Uttley L, et al. Systematic Review of Trends in the Incidence Rates of Thyroid Cancer. Thyroid. 2016 Nov;26(11):1541-52.
  38. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2021/cancer-facts-and-figures-2021.pdf. Accessed May 12, 2021.
  39. Wang L, Tian Z, Yang Q, et al. Sulforaphane inhibits thyroid cancer cell growth and invasiveness through the reactive oxygen species-dependent pathway. Oncotarget. 2015 Sep 22;6(28):25917-31.
  40. Yao H, Wang H, Zhang Z, et al. Sulforaphane inhibited expression of hypoxia-inducible factor-1alpha in human tongue squamous cancer cells and prostate cancer cells. Int J Cancer. 2008 Sep 15;123(6):1255-61.
  41. Fahey JW, Kensler TW. The Challenges of Designing and Implementing Clinical Trials With Broccoli Sprouts... and Turning Evidence Into Public Health Action. Front Nutr. 2021 2021-April-29;8(183):648788.
  42. Fahey JW, Zhang Y, Talalay P. Broccoli sprouts: an exceptionally rich source of inducers of enzymes that protect against chemical carcinogens. Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10367-72.