Evaluation of the antileukemic effects of neurokinin-1 receptor antagonists, aprepitant, and L-733,060, in chronic and acute myeloid leukemic cells

DİKMEN M., Gokhaner G., CANTÜRK Z.

ANTI-CANCER DRUGS, cilt.30, sa.7, ss.693-705, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 30 Sayı: 7
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1097/cad.0000000000000769
  • Dergi Adı: ANTI-CANCER DRUGS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.693-705
  • Anahtar Kelimeler: antileukemia, apoptosis, aprepitant, HL-60, K562, L-733,060, neurokinin-1 receptor, NK-1 RECEPTOR, SUBSTANCE-P, GASTROINTESTINAL CANCER, ANTITUMOR ACTION, FLOW-CYTOMETRY, ASSAY
  • Anadolu Üniversitesi Adresli: Evet

Özet

Neurokinin-1 receptor (NK1R) antagonists are known for their anxiolytic, antiemetic, anticancer, and antiinflammatory effects. Aprepitant is used in vomiting and nausea, which are the most common side-effects of patients undergoing chemotherapy for cancer. L-733,060 has been shown to have anxiolytic and antidepressant effects in animal studies and anticancer effect in in-vitro studies. Previous anticancer activity studies with NK1R antagonists have reported that NK-1 antagonists have an antitumoral activity on gastric carcinoma, larynx carcinoma, retinoblastoma, hepatocarcinoma, glioma, neuroblastoma, and osteoblastoma cells. In this study, we have aimed to show and compare the antileukemic effects of aprepitant and L-733,060 on acute and chronic myeloid leukemic cells by using in-vitro experiments, such as WST-1, cell imaging, annexin-V binding, soft agar colony formation, and Hoescht staining. As a result, we have determined that both aprepitant and L-733,060 had strong antiproliferative effects on K562 and HL-60 cells. Moreover, the two drugs caused significant apoptosis and decreased colony forming depending on concentration increase. These findings suggested that NK1R antagonists exhibited antileukemic activities and may be considered to have a novel therapeutic potential for acute and chronic myeloid leukemia. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved.