Kaempferol sensitizes tumor necrosis factor-related apoptosis-inducing ligand-resistance chronic myelogenous leukemia cells to apoptosis

Raedeh Saraei, Heshu Sulaiman Rahman, Masoud Soleimani, Mohammad Asghari-Jafarabadi, Adel Naimi, Ali Hassanzadeh, Saeed Solali

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5 Citations (Scopus)

Abstract

Background: The tumor necrosis factor (TNF)-related apoptosis-inducing ligand, TRAIL, an apoptosis-inducing cytokine, has attracted much attention in the treatment of cancer for its selective toxicity to malignant rather than normal cells. However, the apoptosis-inducing ability of TRAIL is weaker than expected primarily due to cancer cell resistance. As one of the dietary flavonoids, kaempferol, has been shown to be antiproliferative and might have a protective effect against TRAIL resistance, particularly for hematologic malignancies. Methods and results: Here, we studied the potential of kaempferol to enhance the TRAIL-induced cytotoxicity and apoptosis in human chronic myelogenous leukemia (CML) cell line K-562, as well as the expression of specific genes with impact on TRAIL signal regulation. Analysis of flowcytometry data showed that treatment with kaempferol did enhance sensitivity of CML cells to pro-apoptotic effects of anti-TRAIL antibody. Although the gene expression levels were heterogeneous, cFLIP, cIAP1 and cIAP2 expression were generally downregulated where co-treatment of kaempferol and TRAIL was employed and these effects appeared to be dose-dependent. We further demonstrated that the expression of death receptors 4 and 5 tended to increase subsequent to the combination treatment. Conclusions: Consequently, it is reasonable to conclude that sensitization of chronic leukemia cells to TRAIL by kaempferol in vitro should be considered as a way of focusing clinical attention on leukemia therapy.

Original languageEnglish
Pages (from-to)19-29
Number of pages11
JournalMolecular Biology Reports
Volume49
Issue number1
DOIs
Publication statusPublished - Jan 2022
Externally publishedYes

Keywords

  • cFLIP
  • Chronic myelogenous leukemia (CML)
  • cIAP
  • Death receptors
  • Kaempferol
  • Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)

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