Antitumor activity of a novel dual functional podophyllotoxin derivative involved PI3K/AKT/mTOR pathway

Autoři: Yongli Li aff001;  Tengfei Huang aff002;  Yun Fu aff002;  Tingting Wang aff002;  Tiesuo Zhao aff002;  Sheng Guo aff002;  Yanjie Sun aff003;  Yun Yang aff002;  Changzheng Li aff002
Působiště autorů: College of Basic Medical Science, Sanquan College of Xinxiang Medical University, Xinxiang, Henan, P. R. China aff001;  College of Basic Medical Science, Xinxiang Medical University, Xinxiang, Henan, P. R. China aff002;  Experimental Teaching Center of Biology and Basic Medicine, Sanquan College of Xinxiang Medical University, Xinxiang, Henan, P. R. China aff003
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0215886


The progression of cancer through local expansion and metastasis is well recognized, but preventing these characteristic cancer processes is challenging. To this end, a new strategy is required. In this study, we presented a novel dual functional podophyllotoxin derivative, 2-pyridinealdehyde hydrazone dithiocarbamate S-propionate podophyllotoxin ester (PtoxPdp), which inhibited both matrix metalloproteinases and Topoisomerase II. This new podophyllotoxin derivative exhibited significant anti-proliferative, anti-metastatic that correlated with the downregulation of matrix metalloproteinase. In a xenograft animal local expansion model, PtoxPdp was superior to etoposide in tumor repression. A preliminary mechanistic study revealed that PtoxPdp induced apoptosis and autophagy via the PI3K/AKT/mTOR pathway. Furthermore, PtoxPdp could also inhibit epithelial–mesenchymal transition, which was achieved by downregulating both PI3K/AKT/mTOR and NF-κB/Snail pathways. Taken together, our results reveal that PtoxPdp is a promising antitumor drug candidate.

Klíčová slova:

Apoptosis – Autophagic cell death – Cancer treatment – Hepatocellular carcinoma – Metastasis – Metastatic tumors – Mouse models – Lysosomes


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