Quercetin sensitizes human myeloid leukemia KG‐1 cells against TRAIL‐induced apoptosis

• Published in: Journal of cellular physiology 2019-08, Vol.234 (8), p.13233-13241
• Main Authors: Naimi, Adel, Entezari, Atefeh, Hagh, Majid Farshdousti, Hassanzadeh, Ali, Saraei, Raedeh, Solali, Saeed
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; acute myeloid leukemia (AML); Adults; Annexin V; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Apoptosis; Apoptosis - drug effects; Cancer; Cell Line, Tumor; Cytotoxicity; Drug Synergism; Gene expression; Genes; Humans; Iodides; Leukemia; Leukemia, Myeloid, Acute - pathology; Myeloid leukemia; Propidium iodide; Proteins; Quercetin; quercetin (QUR); Quercetin - pharmacology; Ribonucleic acid; RNA; Sensitizing; Side effects; TNF-Related Apoptosis-Inducing Ligand - pharmacology; TNF‐related apoptosis‐inducing ligand (TRAIL); Toxicity; TRAIL protein; Tumor cells; Tumor necrosis factor
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.27995

Introduction Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Conventional treatments are associated with cytotoxicity and systemic side effects. Hence, efforts in the field of cancer treatment are focused on finding the strategies which can specifically target the tumor cells without affecting the normal cells. TNF‐related apoptosis‐inducing ligand (TRAIL) is a biological cytokine which has the mentioned specificity, but the resistance of some cancer cells limits its use as a therapeutic strategy. Recent studies have shown that quercetin (QUR) can be used as a sensitizing agent alongside with TRAIL. The present study showed that QUR can increase the effect of TRAIL‐induced cytotoxicity in KG‐1 cells. Materials and Methods In this descriptive study, the IC50 dose for QUR in the KG‐1 cell line was first determined by 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide assay. Then, the cells were treated with TRAIL and QUR for 12, 24, and 48 hr. The rate of apoptosis was measured by Annexin V/propidium iodide assay. Also, the molecular evaluation of candidate genes was accomplished before and after the treatment. Results The results indicated that QUR could sensitize the KG‐1 cells against the TRAIL‐induced apoptosis. This outcome is achieved by increasing the messenger RNA expression levels of the death receptor genes and reducing the expression of antiapoptotic proteins, as well as decreasing the expression of the NF‐κB subunit. Conclusion Our findings suggest that QUR can sensitize the acute myeloid KG‐1 cells against TRAIL. Moreover, the combinational therapy of these agents might promisingly improve the clinical efficacy of TRAIL in patients with AML.