Dihydroartemisinin induces autophagy-dependent death in human tongue squamous cell carcinoma cells through DNA double-strand break-mediated oxidative stress.

Oncotarget
Xinli ShiMingrui Zhou

Abstract

Dihydroartemisinin is an effective antimalarial agent with multiple biological activities. In the present investigation, we elucidated its therapeutic potential and working mechanism on human tongue squamous cell carcinoma (TSCC). It was demonstrated that dihydroartemisinin could significantly inhibit cell growth in a dose- and time-dependent manner by the Cell Counting Kit-8 and colony formation assay in vitro. Meanwhile, autophagy was promoted in the Cal-27 cells treated by dihydroartemisinin, evidenced by increased LC3B-II level, increased autophagosome formation, and increased Beclin-1 level compared to dihydroartemisinin-untreated cells. Importantly, dihydroartemisinin caused DNA double-strand break with simultaneously increased γH2AX foci and oxidative stress; this inhibited the nuclear localization of phosphorylated signal transducer and activator of transcription 3 (p-STAT3), finally leading to autophagic cell death. Furthermore, the antitumor effect of dihydroartemisinin-monotherapy was confirmed with a mouse xenograft model, and no kidney injury associated with toxic effect was observed after intraperitoneal injection with dihydroartemisinin for 3 weeks in vivo. In the present study, it was revealed that dihydroartemi...Continue Reading

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Citations

Nov 20, 2019·Medicinal Research Reviews·Tuhina KhanGiuseppe Campiani
Apr 25, 2020·International Journal of Molecular Sciences·Qingya ShiIvet Bahar
Apr 12, 2019·Medicinal Research Reviews·Xin SunJianbin Zhang
Jul 17, 2021·Apoptosis : an International Journal on Programmed Cell Death·Chirine El-BabaNadine Darwiche
Oct 24, 2020·European Journal of Pharmacology·Seyed Ali MosaddadHamid Tebyanian

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Methods Mentioned

BETA
transmission electron microscopy
fluorescence microscopy
nuclear translocation
xenograft
xenografts
dissection
confocal microscopy

Software Mentioned

SOFTmax PRO
SPSS19

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