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.
Highlights
Colorectal cancer (CRC) is the third most common cancer worldwide, with estimated annual deaths of more than 500,000
The Cyanidin chloride (CyCl) treatment resulted in a significant decrease in cell proliferation in a time- and dose-dependent manner in all colon cancer cells compared to the treatment with dimethyl sulfoxide (DMSO) (p < 0.05) (Figure 1)
To determine whether apoptosis induction contributed to the inhibitory effect of CyCl on cell viability, we analyzed the apoptotic effect of CyCl on three colon cancer HCT116, HT29, and SW620 cells using flow cytometry analysis
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide, with estimated annual deaths of more than 500,000. When cells are stimulated by pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), the IκB protein is phosphorylated by the IκB kinases (IKK) complex and NF-κB translocates to the nucleus, increasing the expression of the target genes [3]. Such a substance that increases NF-κB activity induces reactive oxygen species (ROS) formation, and ROS play a central role in regulating the expression of genes involved in the growth, survival, and metastasis of cancer cells by activating NF-κB transcription factors [4]. The production of excessive ROS in the intestinal lumen causes the cells to expose oxidative stress, thereby inducing cellular damage and contributing to the onset of the disease [5]
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