br Conclusion br We formulated MP PPPD micelles
We formulated MP/PPPD micelles to deliver the mainly active gene of VSV for colon cancer treatment without virulence of the virus. This nano-delivery system was proven to have a high transfection eﬃciency of MP plasmid. MP synthesized in host NSC232003 could prominently inhibit tumor growth through mechanisms of direct cycotoxicity and apoptosis. The formation of MP/PPPD micelles is promising for future clinical application.
Conflicts of interest
The authors report no conflict of interest in this study.
This research was supported by the Ministry of Science and Technology of the People's Republic of China (No. 2018ZX09201018-
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Anti-lung cancer activity and inhibitory mechanisms of a novel Calothrixin T A derivative
Xiaohong Yang, Jiangsheng Gao, Jian Guo, Zimeng Zhao, Shao-Lin Zhang , Yun He
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, 55 South Daxuecheng Road, Chongqing 401331, PR China
Topo I inhibitor
Cell cycle arrest
Aims: CAA45 is a calothrixin A (CAA) analogue with anti-cancer activity at nanomolar concentration. This study aimed to investigate the anti-lung cancer activity of CAA45 and explore its mechanisms of actions.
Main methods: CAA and CAA45 were synthesized and their inhibition on DNA topoisomerase I (Topo I) per-formed by evaluating the relaxation of supercoiled pBR322 plasmid DNA and their anti-lung cancer capacity determined by cytotoxic assays, cell migration, cell cycle, cell apoptosis, cell autophagy and related signaling proteins expression by western blot.
Key findings: CAA45 significantly inhibited human non-small cancer cell A549 and NCI-H1650 cells growth with IC50 values of 110 and 230 nM, respectively. In the A549 xenograft models, CAA45 displayed strong antitumor activities at a dose of 10 mg/kg. CAA45 inhibited Topo I activity and caused the cell cycle arrest at S phase, which also reduced A549 cell migration by inhibiting MMP-2 and MMP-9 expressions. Furthermore, CAA45 induced A549 cell apoptosis and autophagy. The apoptosis pathway was involved in the release of cytochrome c and caspase activation. CAA45 also inhibited Akt, activated JNK and up-regulated p53 signals in A549 cells, which may serve as a modulator to induce apoptosis and autophagy in cancer cells.