Abstract
BackgroundDehydrodiisoeugenol (DEH), a novel lignan component extracted from nutmeg, which is the seed of Myristica fragrans Houtt, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. However, the mechanism of its anticancer activity in gastrointestinal cancer remains to be investigated.MethodsIn this study, the anticancer effect of DEH on human colorectal cancer and its underlying mechanism were evaluated. Assays including MTT, EdU, Plate clone formation, Soft agar, Flow cytometry, Electron microscopy, Immunofluorescence and Western blotting were used in vitro. The CDX and PDX tumor xenograft models were used in vivo.ResultsOur findings indicated that treatment with DEH arrested the cell cycle of colorectal cancer cells at the G1/S phase, leading to significant inhibition in cell growth. Moreover, DEH induced strong cellular autophagy, which could be inhibited through autophagic inhibitors, with a rction in the DEH-induced inhibition of cell growth in colorectal cancer cells. Further analysis indicated that DEH also induced endoplasmic reticulum (ER) stress and subsequently stimulated autophagy through the activation of PERK/eIF2α and IRE1α/XBP-1 s/CHOP pathways. Knockdown of PERK or IRE1α significantly decreased DEH-induced autophagy and retrieved cell viability in cells treated with DEH. Furthermore, DEH also exhibited significant anticancer activities in the CDX- and PDX-models.ConclusionsCollectively, our studies strongly suggest that DEH might be a potential anticancer agent against colorectal cancer by activating ER stress-induced inhibition of autophagy.
Highlights
Dehydrodiisoeugenol (DEH), a novel lignan component extracted from nutmeg, which is the seed of Myristica fragrans Houtt, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases
DEH inhibits the proliferation of colorectal cancer cells in vitro Dehydrodiisoeugenol (DEH, CAS: 83377–50–8), known as isoeugenol or diisoeugenol, is a benzofuran-type neolignane extracted from Myristica fragrans Houtt, which has been prescribed in Chinese medicine for a long time [33]
The results showed that DEH could inhibit colorectal cancer cell lines HCT 116 and SW620 in a time- and dose-dependent manner (Fig. 1b)
Summary
Dehydrodiisoeugenol (DEH), a novel lignan component extracted from nutmeg, which is the seed of Myristica fragrans Houtt, displays noticeable anti-inflammatory and anti-allergic effects in digestive system diseases. To aggravate the situation further, the absorption function of the intestine is reduced, due to abnormalities in the intestinal mucosa [13] This situation leads to diarrhea, abdominal pain, and other adverse symptoms that eventually affect the normal life of the patients [14]. It is worthwhile to explore more effective and non-toxic drugs for the treatment of colorectal cancer [18]. This strategy could be beneficial in improving the quality of life of the patients [19,20,21]
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