Abstract
Sulforaphane (SFN), which is highly enriched in cruciferous vegetables, has been investigated for its cancer chemopreventive properties and ability to induce autophagy. Uridine 5′-diphospho (UDP)-glucuronosyltransferase (UGT)1A induction is one of the mechanisms that is responsible for the cancer chemopreventive activity of SFN. The current study demonstrates that rapamycin may enhance the chemopreventive effects of SFN on Caco-2 cells; this may be partially attributed to nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2)- and human pregnane X receptor (hPXR)-mediated UGT1A1, UGT1A8 and UGT1A10 induction. These results indicate that targeting autophagy modulation may be a promising strategy for increasing the chemopreventive effects of SFN in cases of colon cancer.
Highlights
Previous epidemiological studies have indicated that dietary intake of cruciferous vegetables may protect against multiple cancers and their protective effects are partially credited toKey words: uridine 5'-diphospho‐glucuronosyltransferase 1A, Caco‐2 cells, sulforaphane, chemoprevention, cytochrome P450 3A4, autophagy chemopreventive phytochemicals, isothiocyanates (ITCs) [1,2]
The present study demonstrated that a dose‐dependent increase in light chain 3 (LC3)‐II expression levels may be induced in Caco‐2 cells by treatment with SFN at concentrations ranging from 5 to 25 μM, and LC3‐positive punctate staining (LC3‐II) levels may be increased in a time‐dependent manner by incubation with 25 μM SFN for 6‐36 h
To evaluate the potential role of autophagy in SFN‐mediated cancer chemoprevention, Caco‐2 cells were treated with SFN in combination with 3‐MA or rapamycin
Summary
Previous epidemiological studies have indicated that dietary intake of cruciferous vegetables may protect against multiple cancers and their protective effects are partially credited to. With respect to phase I enzyme metabolism, SFN has been demonstrated to decrease the enzyme activities of cytochromes P450 (CYPs) 1A1 and 2B1/2 in rat hepatocytes, as well as CYP3A4 in human hepatocytes [5]. The majority of SFN studies have focused on phase II enzyme induction via the Keap1‐nuclear factor erythroid 2-related factor 2 (Nrf2)‐antioxidant response element (ARE) signaling pathways. SFN has been demonstrated to induce phase II enzymes, namely glutathione‐S‐transferase (GST), nicotinamide adenine dinucleotide phosphate quinine oxidoreductase and uridine 5'‐diphospho (UDP)‐glucuronosyltransferase (UGT) [3]. UGT, the representative member of the phase II enzyme family, conjugates endogenous and exogenous substrates with a β‐glucuronic acid moiety. Following glucuronidation, these compounds are more water soluble and excreted [7]. UGT1A1 is a major isoform of the UGT1A family and is the only isoform with bilirubin glucuronidating
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