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Author Notes:

CONTACT: Abdel Kareem Azab, PhD, B. Pharm., Assistant Professor, aazab@radonc.wustl.edu, Department of Radiation Oncology, Cancer Biology Division, Washington University in Saint Louis School of Medicine, 4511 Forest Park Ave., Room 3103, St. Louis, MO 63108, USA

Authors’ contributions: P.P. designed the study, performed experiments, analyzed, interpreted the data and wrote the manuscript; F.A. performed experiments and evaluated the data; B.M. and M.L. evaluated the data, and reviewed the manuscript; A.K.A and J.A designed and supervised the study, interpreted the data and edited the manuscript.

All authors reviewed and approved the manuscript.

Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article

Dr Arbiser is listed as inventor on US patent 8030299.

Dr Azab receives research support from Verastem, Selexys, Karyopharm and Cell Works, and is the founder and owner of Targeted Therapeutics LLC.

Other authors state no conflicts of interest.

Subjects:

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Hematology
  • Tris DBA
  • Src
  • multiple myeloma
  • drug resistance
  • hypoxia
  • SRC-FAMILY KINASES
  • TUMOR PROGRESSION
  • PROMOTES DISSEMINATION
  • SIGNAL-TRANSDUCTION
  • PROTEIN-KINASE
  • CELL-LINES
  • ACTIVATION
  • CANCER
  • EXPRESSION
  • INHIBITOR

Tris DBA palladium overcomes hypoxia-mediated drug resistance in multiple myeloma

Tools:

Journal Title:

Leukemia & Lymphoma

Volume:

Volume 57, Number 7

Publisher:

, Pages 1677-1686

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Despite recent progress in novel and targeted therapies, multiple myeloma (MM) remains a therapeutically challenging incurable disease. The regulation of important cellular processes and its link to cancer presented Src as an attractive target for MM. We suggest a novel strategy to improve the treatment of MM and overcome the drug resistance for the current therapeutic agents by specific inhibition of Src in MM cells by Tris (Dibenzylideneacetone) dipalladium (Tris DBA). Tris DBA reduces proliferation, induces G1 arrest and apoptosis in MM cells. Tris DBA showed additive effect with proteasome inhibitors reducing proliferation, cell cycle signaling, and increasing apoptosis more than each drug alone. Tris DBA overcame hypoxia-induced effects such as enhanced chemotaxis or drug resistance to proteasome inhibitors by inhibition of HIF1α expression. Moreover, we found that Tris DBA is an effective anti-myeloma agent alone or in combination with other targeted drugs and that it reverses hypoxia-induced drug resistance in myeloma.

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© 2015 Informa UK Limited, trading as Taylor & Francis Group

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