Abstract
Effective chemotherapy drugs for colorectal cancer remain a challenge. In this research, Ziyuglycoside II (Ziyu II), exhibits considerable antitumor activity against CRC cells both in vitro and in vivo. The results showed that Ziyu II induced apoptosis through the accumulation of reactive oxygen species (ROS), which was necessary for Ziyu II to inhibit colorectal cancer cells. Intriguingly, The treatment of Ziyu II triggered complete autophagic flux in CRC cells. Inhibition of autophagy partially reversed Ziyu II-induced growth inhibition, demonstrating a cytotoxic role of autophagy in response to Ziyu II-treated. Mechanism indicated that Ziyu II-induced autophagy by inhibiting Akt/mTOR pathway. Akt reactivation partially reduced Ziyu II-induced LC3-II turnover and LC3 puncta accumulation. Especially, Ziyu II improves the sensitivity of 5-fluorouracil which is the first-line chemotherapy drug in colorectal cancer cells. This research provides novel insight into the molecular mechanism of Ziyu II’s anti-proliferation, including apoptosis and autophagy, and lays a foundation for the potential application of Ziyu II in clinical CRC treatment.
Highlights
Colorectal cancer (CRC) has been associated as the most generally diagnosed cancers worldwide, with the number of new cases relinquished 1.85 million in 2018, accounting for 9.2% of all cancerrelated deaths (Siegel et al, 2017; Bray et al, 2018)
The results showed that Ziyu 3b-3-a-L-arabinopyranosyloxy-19-hydroxyurs-12-en-28-oic acid (II) induced apoptosis through the accumulation of reactive oxygen species (ROS), which was necessary for Ziyuglycoside II (Ziyu II) to inhibit colorectal cancer cells
As pieces of evidence highlighted the important role of druginduced autophagy in cancer treatment (Cui et al, 2018; Poillet-Perez et al, 2018; Deng et al, 2019), we examined whether autophagy is involved in Ziyu II-induced CRC cell death
Summary
Colorectal cancer (CRC) has been associated as the most generally diagnosed cancers worldwide, with the number of new cases relinquished 1.85 million in 2018, accounting for 9.2% of all cancerrelated deaths (Siegel et al, 2017; Bray et al, 2018). Screening for colorectal cancer remains the most significant and cost-effective maneuvering to diminish the incidence rate and mortality of the illness, but it still lacks the screening programs in the developing countries (Kuipers et al, 2015; Onyoh et al, 2019). Surgery, radiotherapy, and adjuvant chemotherapy have greatly improved the survival rate of colorectal cancer, but there are some obstacles in the application of chemotherapy, such as lack of selectivity, insufficient drug concentrations in tumor tissues, the emergence of drug-resistant cancer cells, and inevitable systemic toxicity (Geng et al, 2017). Novel agents with rare or no by-effects are urgently needed to improve the prognosis of CRC patients
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.
