Quercetin and sulforaphane in combination suppress the progression of melanoma through the down-regulation of matrix metalloproteinase-9

Abstract

Abstract. malignant melanoma is one of the most common types of cancer in the uS and worldwide. the epidemiological data suggest that dietary modification may reduce the incidence of this disease. Quercetin (3,5,7,3',4'-tetrahydroxyflavone), a flavonoid isolated from onion, exhibits anti-oxidant, anti-inflammatory and anti-cancer effects. D,L-sulforaphane [1-isothiocyanato-4-(methylsulfinyl)-butane], a cruciferous vegetable-derived isomer isolated from broccoli, is highly effective in protection against cancer. Matrix metalloproteinases (MMPs), extracellular matrix degrading enzymes, are involved in embryogenesis, inflammation, angiogenesis and cancer. mmp-9 in particular plays a crucial role in the regulation of invasion, tumor growth and metastasis. Previous studies have reported that both quercetin and sulforaphane independently reduce tumor growth and metastasis in breast, prostate, lung and other types of cancers. However, the combined effects of quercetin and sulforaphane on the regulation of tumor growth and the mechanism(s) of actions underlying this process have not yet been investigated. In the present study, we report for the first time that quercetin and sulforaphane in combination inhibit the proliferation and migration of melanoma (B16F10) cells more effectively than either compound used alone. Moreover, these compounds in combination significantly suppressed melanoma growth as compared to their individual use in a mouse model. This combined effect was predominantly due to a decrease in mmp-9 expression in the mouse tumors. taken together, our findings revealed that the administration of quercetin and sulforaphane in combination rather than alone may be a more effective approach for the treatment of malignant melanoma. Introductionmalignant melanoma is one of the most common types of cancer in the US as well as worldwide. It is an aggressive disease with high metastatic potential and resistance to many cytotoxic agents (1). Melanoma cells have low levels of spontaneous apoptosis, and chemotherapeutic drugs function by inducing apoptosis (1). Many dietary agents, including kinase inhibitors, have been inversely correlated to the spread of malignant melanoma (2-4). The alkylating agent dacarbazine is currently being used in clinical trials in combination with novel therapeutic agents (4). Quercetin (3,5,7,3' ,4'-tetrahydroxyflavone) is a flavonoid isolated from onion, whereas sulforaphane [1-isothiocyanato-4-(methylsulfinyl)-butane] is a member of an isothiocyanate family of chemopreventive agents isolated from broccoli. The anti-cancer properties of these compounds have been demonstrated in a number of malignancies, including prostate, breast, skin and liver cancers (5-9). Previous reports suggest that quercetin is an anti-oxidant and anti-inflammatory compound (10,11). Others have indicated that sulforaphane acts as a potential HDAC inhibitor and an inducer of various pro-apoptotic molecules (12)(13)(14). Sulforaphane was also found to inhibit prostate tumor growth and lung metastasis in a melanoma...

Dietary Sulforaphane in Cancer Chemoprevention: The Role of Epigenetic Regulation and HDAC Inhibition

“…Pancreatic stem cells and their self-renewal capacity may also be modulated with a combination of sulforaphane and the dietary polyphenol, quercetin (267,319). The synergistic effect of this combination has also been observed in melanoma B16F10 cells, with the suppression of proliferation and migration due to an implicated decrease in MMP-9 expression (221).…”

MAPK Genes Interact with Diet and Lifestyle Factors to Alter Risk of Breast Cancer: The Breast Cancer Health Disparities Study

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Diet-Based Strategies for Cancer Chemoprevention: The Role of Combination Regimens Using Dietary Bioactive Components

“…Substantial reductions in the growth of mouse melanoma (B16F10) cells in vitro and in vivo with diminished MMP-9 expression were observed following a combination treatment of sulforaphane plus quercetin. The combination treatment showed strong inhibitory effects on melanoma both in vitro and in vivo, and these effects were stronger than those of each individual treatment (Pradhan et al 2010). Combinations of S-allylcysteine (an organosulfur component in garlic) and lycopene in vivo produced a greater induction of apoptosis in gastric cancer of Wistar rats in comparison to individual treatments (Velmurugan et al 2005).…”