Cell death mechanisms induced by synergistic effects of halofuginone and artemisinin in colorectal cancer cells

Rui Hong Gong, Da Jian Yang, Hiu Yee Kwan, Ai Ping Lyu, Guo Qing Chen*, Zhao Xiang Bian*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Our previous study found that the combination of halofuginone (HF) and artemisinin (ATS) synergistically arrest colorectal cancer (CRC) cells at the G1/G0 phase of the cell cycle; however, it remains unclear whether HF-ATS induces cell death. Here we report that HF-ATS synergistically induced caspase-dependent apoptosis in CRC cells. Specifically, both in vitro and in vivo experiments showed that HF or HF-ATS induces apoptosis via activation of caspase-9 and caspase-8 while only caspase-9 is involved in ATS-induced apoptosis. Furthermore, we found HF or HF-ATS induces autophagy; ATS can't induce autophagy until caspase-9 is blocked. Further analyzing the crosstalk between autophagic and caspase activation in CRC cells, we found autophagy is essential for activation of caspase-8, and ATS switches to activate capase-8 via induction of autophagy when caspase-9 is inhibited. When apoptosis is totally blocked, HF-ATS switches to induce autophagic cell death. This scenario was then confirmed in studies of chemoresistance CRC cells with defective apoptosis. Our results indicate that HF-ATS induces cell death via interaction between apoptosis and autophagy in CRC cells. These results highlight the value of continued investigation into the potential use of this combination in cancer therapy.

Original languageEnglish
Pages (from-to)175-185
Number of pages11
JournalInternational Journal of Medical Sciences
Volume19
Issue number1
DOIs
Publication statusPublished - Jan 2022

Scopus Subject Areas

  • Medicine(all)

User-Defined Keywords

  • halofuginone
  • artemisinin
  • synergy
  • colorectal cancer
  • apoptosis
  • autophagy

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