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:
https://doi.org/10.1371/journal.pone.0215886
Souhrn
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
Zdroje
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Článek vyšel v časopise
PLOS One
2019 Číslo 9
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