Small interfering RNAs targeting cyclin D1 and cyclin D2 enhance the cytotoxicity of chemotherapeutic agents in mantle cell lymphoma cell lines

Katrin Tiemann, Jessica V. Alluin, Anja Honegger, Pritsana Chomchan, Shikha Gaur, Yen Yun, Stephen J. Forman, John J. Rossi, Robert W. Chen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Cyclin D1 (CCND1) is a known cell cycle regulator whose overexpression is a hallmark of mantle cell lymphoma (MCL). Although molecular techniques have unified the diagnostic approach to MCL, no therapeutic advances have been made to target this particular pathway. The significance of CCND1 in the pathogenesis and treatment of MCL has yet to be defined. We have taken advantage of RNA interference (RNAi) to down-regulate CCND1 expression in two MCL cell lines (Granta-519 and Jeko-1) to investigate the cytotoxic effect of combining RNAi with conventional chemotherapeutic agents. We designed four small interfering RNAs (siRNAs) specific to CCND1, one specific to CCND2, and one dual-targeting siRNA that simultaneously down-regulates CCND1 and CCND2. Etoposide and doxorubicin were used as chemotherapeutics in combination with the siRNAs. The transfected siRNAs in MCL cell lines triggered 4060% reduction in target mRNA and protein levels. Importantly, the siRNA-mediated reduction in cyclins resulted in decreased IC50 (50% inhibitory concentration) values for both doxorubicin and etoposide. The combination of siRNA-mediated inhibition of the cyclins along with chemotherapeutic agents could potentially be used to lower the effective doses of the chemotherapeutic agents and reduce drug-related toxicities.

Original languageEnglish
Pages (from-to)2148-2154
Number of pages7
JournalLeukemia and Lymphoma
Volume52
Issue number11
DOIs
Publication statusPublished - Nov 1 2011
Externally publishedYes

Keywords

  • Cell cycle and apoptosis changes
  • Cell lines and animal models
  • Gene therapy
  • Lymphoma and Hodgkin disease

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Small interfering RNAs targeting cyclin D1 and cyclin D2 enhance the cytotoxicity of chemotherapeutic agents in mantle cell lymphoma cell lines'. Together they form a unique fingerprint.

  • Cite this