Efficacy in vitro of caffeine and valproic acid on patient-derived undifferentiated pleomorphic sarcoma and rhabdomyosarcoma cell lines

Kentaro Igarashi, Kei Kawaguchi, Tasuku Kiyuna, Takashi Murakami, Shinji Miwa, Scott D. Nelson, Sarah M. Dry, Yunfeng Li, Arun S. Singh, Hiroaki Kimura, Katsuhiro Hayashi, Norio Yamamoto, Hiroyuki Tsuchiya, Fritz C. Eilber, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Background/Aim: We have previously reported that caffeine (CAF) can enhance chemotherapy efficacy of bone and soft-tissue sarcoma established cell lines via cell-cycle perturbation. We subsequently tested the combination of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, with caffeine on established human osteosarcoma cells in vitro. Both VPA and CAF caused concentration-dependent cell death of the osteosarcoma cell lines in vitro, and their combination was synergistic. We subsequently established patient-derived cell lines from undifferentiated pleomorphic sarcoma (UPS) and rhabdomyosarcoma (RMS), both of which are recalcitrant cancers. These cell lines are termed AC-UPS01 and AC-RMS01, respectively. Materials and Methods: In the present study, we tested CAF and VPA and their combination on the two patientderived sarcoma cell lines. Cell survival after a 72 h exposure to each drug was determined by the WST-8 assay. IC50 values were calculated for each drug. Results: CAF and VPA caused concentration-dependent cytocidal efficacy for both cell lines. The IC50 for CAF for AC-UPS01 was 2.02 ± 0.22 mM. The IC50 for VPA for AC-UPS01 was 9.54 ± 1.44 mM. The IC50 for CAF for AC-RMS01 was 2.37 ± 0.48 mM. The IC50 for VPA for ACRMS01 was 2.13 ± 0.20 mM. Synergistic efficacy of combination treatment of CAF and VPA was also observed for both cell lines. Conclusion: The results of the present study suggest that CAF and VPA may be useful in the treatment of recalcitrant sarcoma.

Original languageEnglish
Pages (from-to)4081-4084
Number of pages4
JournalAnticancer research
Volume37
Issue number8
DOIs
Publication statusPublished - 2017 Aug
Externally publishedYes

Keywords

  • Caffeine
  • Cell kill
  • Patient-derived cell lines
  • RMS
  • Rhabdomyosarcoma
  • Synergy
  • UPS
  • Undifferentiated pleomorphic sarcoma
  • Valproic acid

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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