Effects of Vitamin K3 and K5 on Daunorubicin-resistant Human T Lymphoblastoid Leukemia Cells

Anticancer Res. 2015 Nov;35(11):6041-8.

Abstract

Background/aim: Anticancer efficacy of vitamin K derivatives on multidrug-resistant cancer cells has been scarcely investigated.

Materials and methods: The effects of vitamins K3 and K5 on proliferation of human leukemia MOLT-4 cells and on daunorubicin-resistant MOLT-4/DNR cells were estimated by a WST assay. Apoptotic cells were detected by Annexin V and propidium iodide staining, followed by flow cytometry.

Results: Vitamins K3 and K5 significantly inhibited proliferation of leukemic cells at 10 and 100 μM (p<0.05), and these effects were almost equally observed in both MOLT-4 and MOLT/DNR drug-resistant cells. Vitamin K3 induced cell apoptosis at 10 and 100 μM in both MOLT-4 and MOLT-4/DNR cells (p<0.05). Vitamin K5 also increased apoptotic cells, while rather inducing necrotic cell death.

Conclusion: Vitamins K3 and K5 suppress MOLT-4 and MOLT-4/DNR cell-proliferation partially through induction of apoptosis, and these vitamin derivatives can overcome drug resistance due to P-glycoprotein expression.

Keywords: P-glycoprotein; Vitamin K3; apoptosis; daunorubicin resistance; human T-lymphoblastoid leukemia; vitamin K5.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Antibiotics, Antineoplastic / pharmacology
  • Apoptosis / drug effects*
  • Cell Proliferation / drug effects
  • Daunorubicin / pharmacology*
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Flow Cytometry
  • Humans
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology*
  • Tumor Cells, Cultured
  • Vitamin K 3 / analogs & derivatives*
  • Vitamin K 3 / pharmacology*
  • Vitamins / pharmacology*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antibiotics, Antineoplastic
  • Vitamins
  • Vitamin K 3
  • vitamin k5
  • Daunorubicin