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

• Published in: Molecular biology reports 2022, Vol.49 (1), p.19-29
• Main Authors: Saraei, Raedeh, Rahman, Heshu Sulaiman, Soleimani, Masoud, Asghari-Jafarabadi, Mohammad, Naimi, Adel, Hassanzadeh, Ali, Solali, Saeed
• Format: Article
• Language: English
• Subjects: Animal Anatomy; Animal Biochemistry; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Apoptosis; Apoptosis Regulatory Proteins - genetics; Baculoviral IAP Repeat-Containing 3 Protein - genetics; Biomedical and Life Sciences; c-FLIP protein; CASP8 and FADD-Like Apoptosis Regulating Protein - genetics; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chronic myeloid leukemia; Cytotoxicity; Death receptors; Dose-Response Relationship, Drug; Flavonoids; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Histology; Humans; Inhibitor of Apoptosis Proteins - genetics; K562 Cells; Kaempferol; Kaempferols - pharmacology; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Life Sciences; Ligands; Morphology; Myeloid leukemia; Necrosis; Original Article; TNF-Related Apoptosis-Inducing Ligand - pharmacology; TRAIL protein; Tumor necrosis factor; Tumor necrosis factor-TNF; Ubiquitin-Protein Ligases - genetics
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-021-06778-z

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.