Open Access

Synergistic cytotoxic effects of inorganic phosphate and chemotherapeutic drugs on human osteosarcoma cells

  • Authors:
    • Annamaria Spina
    • Luca Sorvillo
    • Emilio Chiosi
    • Antonietta Esposito
    • Francesca Di Maiolo
    • Luigi Sapio
    • Michele Caraglia
    • Silvio Naviglio
  • View Affiliations

  • Published online on: February 26, 2013     https://doi.org/10.3892/or.2013.2306
  • Pages: 1689-1696
  • Copyright: © Spina et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Novel therapeutic approaches are required for the treatment of osteosarcoma. Combination chemotherapy is receiving increased attention in order to identify compounds that may increase the therapeutic index of clinical anticancer drugs. In this regard, naturally occurring molecules with antitumor activity and with limited toxicity to normal tissues have been suggested as possible candidates for investigation of their synergistic efficacy in combination with antineoplastic drugs. Inorganic phosphate (Pi) is an essential nutrient for living organisms. Relevantly, Pi has emerged as an important signaling molecule capable of modulating multiple cellular functions by altering signal transduction pathways, gene expression and protein abundance in many cell types. Previously, we showed that Pi inhibits proliferation and aggressiveness of U2OS human osteosarcoma cells and that Pi is capable of inducing sensitization of osteosarcoma cells to doxorubicin in a p53-dependent manner. In this study, we extended the role of Pi in the chemosensitivity of osteosarcoma cells to other anticancer drugs. Specifically, we report and compare the antiproliferative effects of a combination between Pi and doxorubicin, Taxol® and 5-fluorouracil (5-FU) treatments. We found that Pi increases the antiproliferative response to both Taxol and doxorubicin to a similar extent. On the other hand, Pi did not potentiate the anticancer effects induced by 5-FU. These effects were paralleled by apoptosis induction and were cell cycle-dependent. The clinical significance of our data and their potential therapeutic applications for improving osteosarcoma treatment are discussed.
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May 2013
Volume 29 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Spina A, Sorvillo L, Chiosi E, Esposito A, Di Maiolo F, Sapio L, Caraglia M and Naviglio S: Synergistic cytotoxic effects of inorganic phosphate and chemotherapeutic drugs on human osteosarcoma cells. Oncol Rep 29: 1689-1696, 2013
APA
Spina, A., Sorvillo, L., Chiosi, E., Esposito, A., Di Maiolo, F., Sapio, L. ... Naviglio, S. (2013). Synergistic cytotoxic effects of inorganic phosphate and chemotherapeutic drugs on human osteosarcoma cells. Oncology Reports, 29, 1689-1696. https://doi.org/10.3892/or.2013.2306
MLA
Spina, A., Sorvillo, L., Chiosi, E., Esposito, A., Di Maiolo, F., Sapio, L., Caraglia, M., Naviglio, S."Synergistic cytotoxic effects of inorganic phosphate and chemotherapeutic drugs on human osteosarcoma cells". Oncology Reports 29.5 (2013): 1689-1696.
Chicago
Spina, A., Sorvillo, L., Chiosi, E., Esposito, A., Di Maiolo, F., Sapio, L., Caraglia, M., Naviglio, S."Synergistic cytotoxic effects of inorganic phosphate and chemotherapeutic drugs on human osteosarcoma cells". Oncology Reports 29, no. 5 (2013): 1689-1696. https://doi.org/10.3892/or.2013.2306