Abstract
The roots of Toddalia asiatica (L.) Lam. (TA) has been often used in Chinese folk medicine to treat different diseases, including but not limited to arthritis, injuries, stomachache, and even tumors. However, the anti-cancer effects and the action mechanisms of TA remain elusive. Therefore, we firstly evaluated the effects of different extracts of TA on the growth of human colon cancer cells, and then tried to further elucidate their underlying molecular mechanisms. As a result, the dichloromethane fraction (DF) was found to possess the highest anti-proliferative activity with IC50 value at 18 μg/mL among all of the four extracts from TA, and strongly inhibited HT-29 cell growth and halted cell cycle progression in G2/M phase. DF also induced phosphatidylserine externalization and activated caspases -8, -9, and -3, suggesting DF induced apoptosis through intrinsic and extrinsic pathways. Furthermore, we found that HT-29 cell cycle arrest induced by DF could be the result of reactive oxygen species (ROS), as the ROS scavenger N-acetyl cysteine (NAC) attenuating it. Taken together, these results indicated that DF induced cell cycle arrest at G2/M phase and apoptosis in HT-29 cells, and could be a promising source for developing natural therapeutics for colon cancer.
Highlights
Toddalia asiatica (L.) Lam. (Rutaceae) (TA) has been widely used as traditional Chinese medicine for the treatment of various diseases in China (Yang et al, 2013; Tong et al, 2014)
To probe whether cell cycle arrest contributed to cell growth suppression by dichloromethane fraction (DF), we firstly evaluated how DF would affect cell cycle distribution in HT-29 cells by propidium iodide (PI) staining, and the DNA content was examined by flow cytometry
Increasing concentration of DF caused a significant increase in cell population at the G2/M phase along with decrease in cell population in G0/G1 and S phase cells. These results showed that DF inhibited the growth of HT-29 cells with cell cycle arrest at G2/M phase
Summary
Toddalia asiatica (L.) Lam. (Rutaceae) (TA) has been widely used as traditional Chinese medicine for the treatment of various diseases in China (Yang et al, 2013; Tong et al, 2014). The pure compounds of TA such as toddaculin, 8-methoxydihydrochelerythrine, 8-methoxynorchelerythrine, skimmiamine, benzo[c]phenanthridine derivatives have been shown to inhibit proliferation in diverse types of human cancer cells derived from different tissue origins in vitro (Iwasaki et al, 2006, 2010; Vázquez et al, 2012; Hirunwong et al, 2016), suggesting that TA extracts or its bioactive components have a good potential for the discovery and development of novel natural anti-cancer therapeutics. Traditional Chinese medicines (TCMs) have played an important part in primary health care in rural areas of China in terms of general availability, considerable curative action, and mild side effects since long time ago, and are becoming an important resource for natural new drug discovery nowadays. Some natural medicines derived from TCMs are even used in clinic for the treatment of various cancers In this context, we strived to discover and develop new, affordable, and effective natural therapeutics from TA for the treatment of colon cancers. We firstly examined the effects of TA extracts on cell cycle development and cell apoptosis, and tried to explore the potential of TA as a useful natural product against colon cancer
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
