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Chemopreventive effect of chalcone derivative, L2H17, in colon cancer development
Shanmei Xu1, Minxiao Chen1, Wenbo Chen2
1Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China. 909313487@qq.com.
Background:
Colon 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.
Methods:
The 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.
Results:
Our 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.
Conclusions:
All these findings show that L2H17 might be a potential growth inhibitory chalcones derivative for colon cancer cells.
Insights
The chalcone derivative L2H17 selectively kills colon cancer cells by inducing cell cycle arrest and apoptosis. This compound also shows anti-tumor activity in vivo, suggesting its potential as a colon cancer treatment.
Area of Science:
- Oncology
- Medicinal Chemistry
Background:
- Colon cancer is a leading cause of cancer mortality worldwide.
- Chalcone derivatives show promise as anti-cancer agents with low mutagenicity.
- Previous studies indicated anti-inflammatory activities of synthesized chalcones.
Purpose of the Study:
- To evaluate the anti-cancer effects of the chalcone derivative L2H17 in colon cancer cells.
- To investigate the molecular mechanisms underlying L2H17's anti-cancer activity.
- To assess the in vivo anti-tumor efficacy of L2H17.
Main Methods:
- Cytotoxicity assessed using MTT and clonogenic assays.
- Cell cycle, apoptosis, migration, and invasion analyzed.
- In vivo anti-tumor effects evaluated in a relevant model.
Main Results:
- L2H17 induced selective G0/G1 cell cycle arrest and apoptosis in colon cancer cells (CT26.WT).
- L2H17 significantly reduced colon cancer cell migration and invasion.
- Compound L2H17 demonstrated marked anti-tumor activity in vivo, involving inactivation of NF-κB and Akt pathways.
Conclusions:
- L2H17 exhibits selective cytotoxic effects on colon cancer cells.
- L2H17 possesses significant anti-tumor properties in vitro and in vivo.
- L2H17 is a potential therapeutic candidate for colon cancer treatment.
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