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Anti-Proliferative Effects of Dendrophthoe pentandra Methanol Extract on BCR/ABL-Positive and Imatinib-Resistant Leukemia Cell Lines

  • Zamani, Afiqah (School of Health Sciences, University Sains Malaysia) ;
  • Jusoh, Siti Asmaa Mat (Department of Haematology, School of Medical Sciences, University Sains Malaysia) ;
  • Al-Jamal, Hamid Ali Nagi (School of Diagnostic and Biomedicine, Faculty of Health Sciences, University of Sultan Zainal Abidin) ;
  • Sul'ain, Mohd Dasuki (School of Health Sciences, University Sains Malaysia) ;
  • Johan, Muhammad Farid (Department of Haematology, School of Medical Sciences, University Sains Malaysia)
  • Published : 2016.11.01

Abstract

Background: Imatinib mesylate, a tyrosine kinase inhibitor specifically targeting the BCR/ABL fusion protein, induces hematological remission in patients with chronic myeloid leukemia (CML). However, the majority of CML patients treated with imatinib develop resistance with prolonged therapy. Dendrophthoe pentandra (L.) Miq. is a Malaysian mistletoe species that has been used as a traditional treatment for several ailments such as smallpox, ulcers, and cancers. Methods: We developed a resistant cell line (designated as K562R) by long-term co-culture of a BCR/ABL positive CML cell line, K562, with imatinib mesylate. We then investigated the anti-proliferative effects of D. pentandra methanol extract on parental K562 and resistant K562R cells. Trypan blue exclusion assays were performed to determine the IC50 concentration; apoptosis and cell cycle analysis were conducted by flow cytometry. Results: D. pentandra extract had greater anti-proliferative effects towards K562R ($IC50=192{\mu}g/mL$) compared to K562 ($500{\mu}g/mL$) cells. Upon treatment with D. pentandra extract at the IC50. concentration: K562 but not K562R demonstrated increase in apoptosis and cell cycle arrest in the G2/M phase. Conclusion: D. pentandra methanol extract exerts potent anti-proliferative effect on BCR/ABL positive K562 cells.

Keywords

D. pentandra;BCR/ABL;K562;imatinib;CML

Acknowledgement

Supported by : Ministry of Higher Education (MOHE)

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