Chemopreventive effect of chalcone derivative, L2H17, in colon cancer development

Abstract

BackgroundColon cancer is the third most commonly diagnosed cancer and the second leading cause of cancer mortality worldwide. Chalcone and its derivatives are reported to exhibit anti-cancer effects in several cancer cell lines, including colon cancer cells. In addition, chalcones have advantages such as poor interaction with DNA and low risk of mutagenesity. In our previous study, a group of chalcone derivatives were synthesized and exhibited strong anti-inflammatory activities. In this study, we evaluated the anti-cancer effects of the chalcone derivative, L2H17, in colon cancer cells.MethodsThe cytotoxicities of L2H17 on various colon cancer cell lines were investigated by MTT and clonogenic assay. Cell cycle and apoptosis analysis were performed to evaluate the molecular mechanism of L2H17-mediated inhibition of tumor growth. Also, scratch wound and matrigel invasion experiments were performed to estimate the cell migration and invasion after L2H17 treatment. Finally, we observed the anti-colon cancer effects of L2H17 in vivo.ResultsOur data show that compound L2H17 exhibited selective cytotoxic effect on colon cancer cells, via inducing G0/G1 cell cycle arrest and apoptosis in CT26.WT cells. Furthermore, L2H17 treatment decreased cell migration and invasion of CT26.WT cells. In addition, L2H17 possessed marked anti-tumor activity in vivo. The molecular mechanism of L2H17-mediated inhibition of tumor promotion and progression were function through inactivated NF-κB and Akt signaling pathways.ConclusionsAll these findings show that L2H17 might be a potential growth inhibitory chalcones derivative for colon cancer cells.

New Chalcone Derivative Inhibits ABCB1 in Multidrug Resistant T-cell Lymphoma and Colon Adenocarcinoma Cells

“…Interestingly, toxicity of 1C against non-cancerous mouse NIH/3T3 and human MRC-5 cells was markedly reduced, which is a crucial parameter to ensure safety of anticancer treatment. Such a preferential action of chalcones against cancer cells and not non-cancer cells has also been documented in other studies (26,(28)(29)(30).…”

A novel chalcone derivative has antitumor activity in melanoma by inducing DNA damage through the upregulation of ROS products

“…Chalcone has various biological activities, including antiinflammatory, antibacterial and antioxidant activities [24,25]. Chalcone has been shown to have a skeletal structure for antitumor treatment, such as lung cancer, colorectal cancer, liver cancer and breast cancer [26][27][28]. Therefore, chalcone derivatives have been widely studied for antitumor pharmacological activities.…”

Chemopreventive effect of 4'‑hydroxychalcone on intestinal tumorigenesis in ApcMin mice

“…Apigenin can induce G 2 /M cell cycle arrest in multiple colon cancer cell lines with decreased expression of cyclin B1 proteins and the cyclin-dependent kinase p34 ( 40 ), and possesses proapoptotic features that are associated with its pro-oxidative effect, leading to the increased production of reactive oxygen species and oxidative stress ( 41 ). A chalcone derivative, L2H17, was previously reported to have cytotoxic effects on colon cancer cell lines through various biological processes, including induction of G 0 /G 1 cell cycle arrest and apoptosis, attenuation of cell migration and invasion, and inactivation of the NF-κB signaling pathway ( 42 ). L2H17 also possesses in vivo antitumor activity, as determined using a xenograft mouse model of colon cancer ( 42 ).…”

“…A chalcone derivative, L2H17, was previously reported to have cytotoxic effects on colon cancer cell lines through various biological processes, including induction of G 0 /G 1 cell cycle arrest and apoptosis, attenuation of cell migration and invasion, and inactivation of the NF-κB signaling pathway ( 42 ). L2H17 also possesses in vivo antitumor activity, as determined using a xenograft mouse model of colon cancer ( 42 ).…”