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Pain Management 2018
Internal Medicine 2018 International Journal of Anesthesiology & Pain Medicine
ISSN: 2471-982X Page 33
March 26-28, 2018
Vienna, Austria
JOINT EVENT
7 t h E d i t i o n o f I n t e r n a t i o n a l C o n f e r e n c e o n
Internal Medicine and Patient Care
&
6 t h E d i t i o n o f I n t e r n a t i o n a l C o n f e r e n c e o n
Pain Management
Volume 4
Background: Mitoxantrone is an anthracenedione derivative,
which functions as DNA intercalating agent. Mitoxantrone has
been proven effective to treat acute myeloid leukaemia (AML)
through topoisomerase-II inhibition. Previous studies suggest
that challenges still emerge due to the side-effects of therapy
and the possible involvement of ATP-binding cassette family
of membrane transporters in mitoxantrone resistance.
Aims: We aim to develop a high performance liquid
chromatography (HPLC) assay, initially, to quantify
mitoxantrone in plasma and cell extracts. This assay will be
used to investigate whether differences in sensitivity of a
panel of AML cell lines towards mitoxantrone is related to
mitoxantrone uptake and/or efflux.
Methods: Stability of mitoxantrone in different conditions was
investigated in validation of the drug with simple, precise, and
reproducible HPLC assay. Initially, growth curves of HL60,
U937, AML-3, and HEL were generated to determine incubation
time and seeding densities for in-vitro cytotoxicity assay with
alamarBlue. Intracellular mitoxantrone uptake experiment was
performed through incubating cells with different mitoxantrone
concentrations for four hours before analyzing the results with
HPLC assay.
Results: Mitoxantrone showed no significant differences
of stability in plasma (p=0.714) and in plasma with ascorbic
acid (p=0.993) after four weeks. HEL showed the highest
mitoxantrone accumulation despite displaying the least
sensitivity towards mitoxantrone compared with HL60, U937,
and AML-3.
Conclusions: Intracellular mitoxantrone concentration does
not appear to be related with sensitivity of a panel of AML cell
lines towards mitoxantrone. Further studies are necessary to
confirm the existence of resistance mechanisms independent
from membrane transporters.
Biography
Maria Satya Paramitha is a Medical Doctor who has completed her Un-
dergraduate study in Faculty of Medicine, Universitas Indonesia. She has
completed her Master’s degree by Research in Cancer from Newcastle Uni-
versity Medical School, United Kingdom. In this project, she was supervised
by Dr. Gareth Veal from Newcastle Cancer Centre Pharmacology Group,
Northern Institute for Cancer Research.
Investigating the pharmacology of mitoxantrone in acute
myeloid leukaemia
Maria Satya Paramitha, Gareth Veal, Philip Berry and Julieann Sludden
Newcastle University, UK
Maria Satya Paramitha et al., Int J Anesth Pain Med 2018, Volume 4
DOI: 10.21767/2471-982X-C1-002