Abstract
BackgroundThe compound 3,3′,4′,5,5′,7-hexahydroxyflavone (myricetin) is a natural flavonoid with antitumour activity. Most of the studies on myricetin have focused on the induction of tumour cell apoptosis, and little is known about the regulatory effects of myricetin on autophagy in colorectal cancer.MethodsHere, we studied the effects of myricetin on colon cancer cell proliferation, apoptosis and autophagy. We detected colon cancer cell apoptosis induced by myricetin via flow cytometry and Hoechst 33258 staining. Transmission electron microscopy was performed to observe the morphological changes associated with autophagy. The expression levels of apoptosis-, autophagy- and PI3K/Akt/mTOR signalling-related proteins were measured by Western blot analysis.ResultsThis study confirmed that myricetin inhibits the proliferation of 4 kinds of colon cancer cell lines. Myricetin induced cell apoptosis and autophagy by inhibiting PI3K/Akt/mTOR signalling pathway. In addition, the inhibition of autophagy with 3-methyladenine (3-MA) promoted the apoptosis of myricetin-treated colon cancer cells.ConclusionsConsidering that myricetin induces apoptosis and autophagy in colon cancer cells, myricetin may become a viable candidate for chemotherapy; it could be used to exert tumour inhibitory effects alone or as adjuvant chemotherapy to inhibit autophagy. These studies may provide further evidence for the potential use of myricetin in the treatment of colon cancer.
Highlights
The compound 3,3′,4′,5,5′,7-hexahydroxyflavone is a natural flavonoid with antitumour activity
The findings demonstrated that myricetin could induce colorectal cancer cell apoptosis and autophagy and that the Phosphatidyl inositide 3-kinase (PI3K)/AKT/Mammalian target of rapamycin (mTOR) signalling pathway might be involved in myricetininduced cell proliferation, apoptosis and autophagy
Western blotting was used to detect the different signalling pathways in HCT116 and SW620 cells treated with myricetin, and the results demonstrated that myricetin-induced cell apoptosis and autophagy were mediated by the PI3K/AKT/mTOR signalling pathway
Summary
The compound 3,3′,4′,5,5′,7-hexahydroxyflavone (myricetin) is a natural flavonoid with antitumour activity. Treatment of colorectal cancer is multifaceted and may include a combination of surgery, radiation therapy, chemotherapy, and targeted therapies such as checkpoint inhibitors and anti-angiogenesis therapies [2]. Myricetin (3,3′,4′,5,5′,7-hexahydroxyflavone) is a natural flavonoid pigment commonly found in fruits, herbs, and nuts [4, 5]. Myricetin differs from other flavonols in the presence of the 3′,4′,5′-trihydroxy. Myricetin has been found to have anticancer properties in a variety of malignancies, including prostate [6], breast [7], gastric [8], and lung cancers [9] (Fig. 1). There are few studies on the role of myricetin in colorectal cancer. Kim et al and Nirmala et al showed that myricetin could inhibit the growth of colorectal cancer in vitro
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