TITLE:
Base Excision Repair Inhibition by Methoxyamine Impairs Growth and Sensitizes Osteosarcoma Cells to Conventional Treatments
AUTHORS:
Ana Paula Montaldi, Julia Alejandra Pezuk, Elza Tiemi Sakamoto-Hojo, Luiz Gonzaga Tone, María Sol Brassesco
KEYWORDS:
Osteosarcoma, Methoxyamine, BER, Cell Lines
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.5 No.4,
March
31,
2014
ABSTRACT: The outcome of patients
with osteosarcoma has not significantly improved in the last three decades.
Therefore, there is still a need for the development of more effective
therapeutic strategies. Methoxyamine (MX) is a base excision repair (BER)
inhibitor that has shown anticancer potential by sensitizing a variety of tumor
cells to ionizing radiation and chemotherapeutic drugs. In the present study, the in vitro antiproliferative effects of MX
were evaluated in two osteosarcoma cell lines, HOS and MG-63. Evaluation of the
influence on radiosensitivity and drug interactions in simultaneous treatments
with methotrexate, doxorubicin, and cisplatin was also performed. Exposure to MX significantly decreased cell
proliferation and mediated a substantial increase of apoptosis. Moreover, our
results showed that MX synergized with ionizing radiation in both cell lines
while potentiated the antitumor
effects of cisplatin and methotrexate. Altogether, the results presented herein
demonstrate the feasibility of inhibiting the BER pathway, which may in future
be a promising strategy for overcoming intrinsic tumor resistance and to
improve the outcome of patients with osteosarcoma.