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Pancreatic Cancer Combination Therapy Using a BH3 Mimetic and a Synthetic Tetracycline.
Quinn, Bridget A; Dash, Rupesh; Sarkar, Siddik; Azab, Belal; Bhoopathi, Praveen; Das, Swadesh K; Emdad, Luni; Wei, Jun; Pellecchia, Maurizio; Sarkar, Devanand; Fisher, Paul B.
Affiliation
  • Quinn BA; Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia.
  • Dash R; Institute of Life Sciences, Bhubaneswar, Orissa, India.
  • Sarkar S; Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia.
  • Azab B; The University of Jordan, Department of Biological Sciences, Amman, Jordan.
  • Bhoopathi P; Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia.
  • Das SK; Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia. VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, Virginia.
  • Emdad L; Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia. VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, Virginia. VCU Massey Cancer Center, Virginia Commonwealth University, School of M
  • Wei J; Sanford-Burnham Medical Research Institute, La Jolla, California.
  • Pellecchia M; Sanford-Burnham Medical Research Institute, La Jolla, California.
  • Sarkar D; Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia. VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, Virginia. VCU Massey Cancer Center, Virginia Commonwealth University, School of M
  • Fisher PB; Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, Virginia. VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, Virginia. VCU Massey Cancer Center, Virginia Commonwealth University, School of M
Cancer Res ; 75(11): 2305-15, 2015 Jun 01.
Article in En | MEDLINE | ID: mdl-26032425
ABSTRACT
Improved treatments for pancreatic cancer remain a clinical imperative. Sabutoclax, a small-molecule BH3 mimetic, inhibits the function of antiapoptotic Bcl-2 proteins. Minocycline, a synthetic tetracycline, displays antitumor activity. Here, we offer evidence of the combinatorial antitumor potency of these agents in several preclinical models of pancreatic cancer. Sabutoclax induced growth arrest and apoptosis in pancreatic cancer cells and synergized with minocycline to yield a robust mitochondria-mediated caspase-dependent cytotoxicity. This combinatorial property relied upon loss of phosphorylated Stat3 insofar as reintroduction of activated Stat3-rescued cells from toxicity. Tumor growth was inhibited potently in both immune-deficient and immune-competent models with evidence of extended survival. Overall, our results showed that the combination of sabutoclax and minocycline was highly cytotoxic to pancreatic cancer cells and safely efficacious in vivo.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Gossypol / Proto-Oncogene Proteins c-bcl-2 / Minocycline Limits: Animals / Humans Language: En Journal: Cancer Res Year: 2015 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pancreatic Neoplasms / Gossypol / Proto-Oncogene Proteins c-bcl-2 / Minocycline Limits: Animals / Humans Language: En Journal: Cancer Res Year: 2015 Document type: Article