Abstract
Glucosinolates (GSL) are naturally occurring β-d-thioglucosides found across the cruciferous vegetables. Core structure formation and side-chain modifications lead to the synthesis of more than 200 types of GSLs in Brassicaceae. Isothiocyanates (ITCs) are chemoprotectives produced as the hydrolyzed product of GSLs by enzyme myrosinase. Benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC) and sulforaphane ([1-isothioyanato-4-(methyl-sulfinyl) butane], SFN) are potential ITCs with efficient therapeutic properties. Beneficial role of BITC, PEITC and SFN was widely studied against various cancers such as breast, brain, blood, bone, colon, gastric, liver, lung, oral, pancreatic, prostate and so forth. Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor limits the tumor progression. Induction of ARE (antioxidant responsive element) and ROS (reactive oxygen species) mediated pathway by Nrf2 controls the activity of nuclear factor-kappaB (NF-κB). NF-κB has a double edged role in the immune system. NF-κB induced during inflammatory is essential for an acute immune process. Meanwhile, hyper activation of NF-κB transcription factors was witnessed in the tumor cells. Antagonistic activity of BITC, PEITC and SFN against cancer was related with the direct/indirect interaction with Nrf2 and NF-κB protein. All three ITCs able to disrupts Nrf2-Keap1 complex and translocate Nrf2 into the nucleus. BITC have the affinity to inhibit the NF-κB than SFN due to the presence of additional benzyl structure. This review will give the overview on chemo preventive of ITCs against several types of cancer cell lines. We have also discussed the molecular interaction(s) of the antagonistic effect of BITC, PEITC and SFN with Nrf2 and NF-κB to prevent cancer.
Highlights
Cancer is one of the deadliest diseases that cause mortality in humans
Benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC) and sulforaphane ([1-isothioyanato4-(methyl-sulfinyl) butane], SFN) are an important ITCs widely studied against various cancer cell lines
Tang et al (2015) showed that BITC treatment inhibits the proliferation of blood cancer cells was correlated with a decrease in the expression of mitogen-activated protein kinase (MAPK) and nuclear transcription factors (TFs) [47]
Summary
Cancer is one of the deadliest diseases that cause mortality in humans. According to the report of 2015, cancer killed about 8.7 millions of people [1]. Myrosinase enzyme catalyzes the hydrolysis process of converting GSL into active substances such as thiocyanates, isothiocyanates (ITCs) and nitrile. ITCs present in crucifer’s vegetables have higher anti-cancerous property and can inhibit cell proliferation [11]. ITCs suppress the cancer cell proliferation by inhibitions of proteins involved in the tumor initiation and proliferation pathways. Higher ITCs disrupt the several steps of carcinogenesis including the prevention of DNA damage in normal cells, stimulate detoxifying enzymes, cell cycle arrest of cancer cells followed by the induced apoptosis [13]. Benzyl isothiocyanate (BITC), phenethyl isothiocyanate (PEITC) and sulforaphane ([1-isothioyanato4-(methyl-sulfinyl) butane], SFN) are an important ITCs widely studied against various cancer cell lines. BITC, PEITC and SFN suppress the tumor growth of various cancer cell lines of breast, brain, blood, bone, colon, gastric, liver, lung, oral, pancreatic, prostate and so forth. Role of ITCs on the regulation of NF-κB via ROS-Nrf2-ARE mediated pathway have discussed elaborately
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