RRC ID 56053
Author Umsumarng S, Mapoung S, Yodkeeree S, Pyne SG, Limtrakul Dejkriengkraikul P.
Title A Pharmacological Strategy Using Stemofoline for more Efficacious Chemotherapeutic Treatments Against Human Multidrug Resistant Leukemic Cells
Journal Asian Pac. J. Cancer Prev.
Abstract Our previous study reported that stemofoline (STF) exhibited a synergistic effect with chemotherapeutic drugs in human multidrug-resistant (MDR) leukemic cells (K526/Adr) by inhibiting the function of P-glycoprotein, which is a membrane transporter that is overexpressed in several types of MDR cancers. This study further investigated the effects of a combination treatment of STF and doxorubicin (DOX) in vitro and in vivo. The combination treatment of 50 mg/kg of STF strongly enhanced the anti-tumor activity of DOX in SCID-beige mice bearing K562/Adr xenografts without additional toxicity when compared to the single treatment groups. Additionally, an examination of the proliferation markers (Ki67) and the apoptotic marker (TUNEL) in tumor tissues in each group revealed that the combination therapy significantly reduced Ki67 positive cells and increased apoptotic cells. From the in vitro experiments we also found that this combination treatment dramatically induced G1 and G2M arrest in K562/Adr when compared to a single treatment of DOX. STF treatment alone did not show any cytotoxic effect to the cells. These results suggest that the accumulation of DOX enhanced by STF was sufficient to induce cell cycle arrest in K562/Adr. These findings support our previous in vitro data and indicate the possibility of developing STF as an adjuvant therapy in cancer treatments.
Volume 19(12)
Pages 3533-3543
Published 2018-12-25
DOI 10.31557/APJCP.2018.19.12.3533
PMID 30583680
PMC PMC6428543
MeSH ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism Animals Apoptosis / drug effects Biomarkers, Tumor / metabolism Cell Cycle / drug effects Cell Cycle Checkpoints / drug effects Cell Line, Tumor Cell Proliferation / drug effects Doxorubicin / pharmacology Drug Resistance, Multiple / drug effects* Drug Resistance, Neoplasm / drug effects* Heterocyclic Compounds, 4 or More Rings / pharmacology* Humans In Situ Nick-End Labeling / methods K562 Cells Ki-67 Antigen / metabolism Leukemia / drug therapy* Leukemia / metabolism Male Mice Mice, Inbred ICR Mice, SCID
Resource
Human and Animal Cells K562/Adr(RCB1898)