A Pharmacological Strategy Using Stemofoline for more Efficacious Chemotherapeutic Treatments Against Human Multidrug Resistant Leukemic Cells
| Autor: | Stephen G. Pyne, Sonthaya Umsumarng, Sariya Mapoung, Supachai Yodkeeree, Pornngarm Limtrakul Dejkriengkraikul |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Combination therapy medicine.medical_treatment Xenograft model Apoptosis Mice SCID P-glycoprotein Heterocyclic Compounds 4 or More Rings Stemofoline Mice 03 medical and health sciences 0302 clinical medicine In vivo Cell Line Tumor Biomarkers Tumor In Situ Nick-End Labeling medicine Animals Humans Chemotherapy Cytotoxic T cell Doxorubicin ATP Binding Cassette Transporter Subfamily B Member 1 Cell Proliferation Mice Inbred ICR Leukemia biology Chemistry Cell Cycle Cell Cycle Checkpoints General Medicine Drug Resistance Multiple In vitro Ki-67 Antigen 030104 developmental biology Drug Resistance Neoplasm 030220 oncology & carcinogenesis biology.protein Cancer research K562 Cells Research Article medicine.drug |
| Zdroj: | Asian Pacific Journal of Cancer Prevention : APJCP |
| ISSN: | 2476-762X |
| DOI: | 10.31557/apjcp.2018.19.12.3533 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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