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Vernodalol enhances TRAIL-induced apoptosis in diffuse large B-cell lymphoma cells

Wenjun Wu1, Yang Yang1, Gang Deng2

  • 1The Bone Marrow Transplantation Center and Multiple Myeloma Treatment Center, The First Affiliated Hospital of Medical College, Zhejiang University, Hangzhou, China.

Molecular Carcinogenesis
|May 4, 2017
PubMed

Insights

Vernodalol, a natural compound, sensitizes diffuse large B-cell lymphoma (DLBCL) cells to TRAIL therapy by increasing death receptor 5 (DR5) and decreasing Mcl-1. This combination therapy shows promise for treating DLBCL.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in cancer cells but faces resistance in many cancers.
  • Enhancing TRAIL efficacy through combination therapy with sensitizers is a key strategy in cancer treatment.

Purpose of the Study:

  • To investigate the potential of vernodalol, a sesquiterpene lactone, as a sensitizer to enhance TRAIL-induced apoptosis in diffuse large B-cell lymphoma (DLBCL).

Main Methods:

  • Utilized small interfering RNA (siRNA) to silence death receptor 5 (DR5) and CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP).
  • Employed a c-Jun N-terminal kinase (JNK) inhibitor to assess the role of JNK activation.
  • Overexpressed induced myeloid leukaemia cell differentiation protein (Mcl-1) to evaluate its impact on apoptosis.
  • Tested the combination therapy in a DLBCL xenograft model.

Main Results:

  • Vernodalol increased DR5 and CHOP expression, sensitizing DLBCL cells to TRAIL-induced apoptosis.
  • DR5 up-regulation was dependent on JNK activation and CHOP induction.
  • Down-regulation of Mcl-1 was crucial for the vernodalol/TRAIL-induced apoptotic effect.
  • The combination of vernodalol and TRAIL inhibited tumor growth in vivo.

Conclusions:

  • Vernodalol acts as a sensitizer for TRAIL therapy in DLBCL by modulating DR5, CHOP, JNK, and Mcl-1 pathways.
  • The combination of TRAIL with vernodalol presents a promising therapeutic strategy for DLBCL.
Keywords:
CHOPDLBCLDR5Mcl-1

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