Cyanidin Chloride Induces Apoptosis by Inhibiting NF-κB Signaling through Activation of Nrf2 in Colorectal Cancer Cells

Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide and a leading cause of cancer-related deaths in developed countries. Anthocyanins are a class of flavonoids, widely distributed in food, exhibiting important biological effects. Cyanidin chloride (CyCl) is the common type of anthocyanin with antioxidative and anti-inflammatory potential. The present study aimed to investigate the molecular mechanisms underlying the chemotherapeutic effects of CyCl in colorectal cancer cells. We found that CyCl treatment induced apoptosis as well as a significant inhibition of cellular proliferation and colony formation in three colon cancer HCT116, HT29, and SW620 cells. In addition, CyCl suppressed nuclear factor-kappa B (NF-κB) signaling and induced the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in tumor necrosis factor-alpha (TNF-α)-stimulated colon cancer cells. Nrf2 and NF-κB are two key transcription factors regulating antioxidative responses and cellular proliferation, respectively. In this study, knockdown of Nrf2 by small interfering RNA (siRNA) transfection inhibited the effect of CyCl on NF-κB signaling and apoptosis, suggesting that there is functional crosstalk between Nrf2 and NF-κB. Our findings demonstrate the important role of Nrf2 in inducing apoptosis through the involvement of NF-κB signaling in colorectal cancer cells, suggesting that CyCl may be used as a potential therapeutic agent for CRC.

Delphinidin and Its Glycosides’ War on Cancer: Preclinical Perspectives

“…The Nrf2 signaling pathway is a key component of the body’s basic defense system against oxidative and electrophilic damage [ 72 ]. Anthocyanins activate a common ARE in the upstream region of their antioxidant genes, regulated by multiple transcription factors, including Nrf2 [ 73 ]. CpG sites in the Nrf promotor region are demethylated as a result of delphinidin activation of Nrf2/ARE, as evidenced by decreased expression of class I/II histone deacetylases and DNA methyltransferases 1 and 3a (DNMT1/3a) ( Table 2 ) [ 26 ].…”

Caragana rosea Turcz Methanol Extract Inhibits Lipopolysaccharide-Induced Inflammatory Responses by Suppressing the TLR4/NF-κB/IRF3 Signaling Pathways

“…In addition, it was found that xanthone can act as vasodilator [44]. Next, cyanin, also known as cyanin chloride or cyanidin-3,5-di-O-glucoside, was reported to induce apoptosis by inhibiting NF-κB signaling through activation of Nrf2 in colorectal cancer cells [45]. Flavocommelin, which is one of the components identified in Commelina communis [46] and was reported to reduce lung damage in influenza virus-infected mice [47].…”

Comparative Analysis of Nutritional Quality of Dendrobium Officinale Kimura Et Migo After Transplantation of Artificially Cultivated Plants From South to North China During Different Growing Years

“…Among them, the two most upregulated avonoids are isorhamnetin-o-gallate and cyanidin chloride, the former is a avonol and belongs to the group of plant secondary metabolites known as avonoids, which have been reported for many biological activities such as antioxidant, anticancer, antimicrobial and anti-in ammatory effects [24] . The latter is one of the most abundant types of anthocyanins and has been shown to have antioxidant properties inhibiting nitric oxide production in many studies [25,26] . Moreover, sinapine was signi cantly upregulated in Peking samples, which led to signi cant improvements in energy, lipid and glucose metabolism in animal models [27][28][29][30] , indicating that sinapine may be an important alkaloid in D. o cinale cultivated in Beijing.…”