Arsenic trioxide potentiates sensitivity of multiple myeloma cells to lenalidomide by upregulating cereblon expression levels.

@article{Jian2017ArsenicTP,
  title={Arsenic trioxide potentiates sensitivity of multiple myeloma cells to lenalidomide by upregulating cereblon expression levels.},
  author={Yuan Jian and Wen Gao and Chuanying Geng and Huixing Zhou and Yun Leng and Yan-chen Li and Wenming Chen},
  journal={Oncology letters},
  year={2017},
  volume={14 3},
  pages={
          3243-3248
        }
}
The mechanism of the anti-myeloma effect of the immunomodulatory drug lenalidomide relies upon the binding of lenalidomide or an analogue to cereblon (CRBN) ubiquitin ligase, which inhibits it and results in the degradation of Ikaros-family zinc finger proteins 1 and 3 (IKZF1 and IKZF3). To determine whether the traditional Chinese medicine arsenic trioxide, could potentiate sensitivity of multiple myeloma (MM) cells to lenalidomide and identify the mechanism by which this happens, the present… 

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References

SHOWING 1-10 OF 17 REFERENCES

The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins

TLDR
It is shown that lenalidomide-bound cereblon acquires the ability to target for proteasomal degradation two specific B cell transcription factors, Ikaros family zinc finger proteins 1 and 3 (IKZF1 and IKZF3).

Cereblon expression is required for the antimyeloma activity of lenalidomide and pomalidomide.

TLDR
CRBN is an essential requirement for IMiD activity and a possible biomarker for the clinical assessment of antimyeloma efficacy andGene expression changes induced by lenalidomide were dramatically suppressed in the presence of CRBN depletion, further demonstrating that CRBN is required for lenalidmide activity.

Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells

TLDR
Using quantitative proteomics, it is found that lenalidomide causes selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKzF3, by the CRBN-CRL4 ubiquitin ligase, which are essential transcription factors in multiple myeloma.

Novel combination of tanshinone I and lenalidomide induces chemo-sensitivity in myeloma cells by modulating telomerase activity and expression of shelterin complex and its associated molecules

TLDR
This maiden in-vitro study provided initial evidences of therapeutic potential of TanI alone or in combination with chemotherapeutic agent Len as novel anticancer agents in myeloma cells which need further evaluation in future.

Mechanisms of action of arsenic trioxide.

TLDR
Substantial data show that arsenic trioxide produces remissions in patients with APL at least in part through a mechanism that results in the degradation of the aberrant PML-retinoic acid receptor alpha fusion protein.

Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma

TLDR
Based on in vitro data, it appears that anti-proliferative effects and downregulation of crucial cytokines are their most important anti-MM attributes.

Current treatment for multiple myeloma.

TLDR
Initial studies both with proteasome inhibitors and with immunomodulatory drugs in patients with relapsed or refractory disease have shown highly encouraging results.

Arsenic trioxide: new clinical experience with an old medication in hematologic malignancies.

  • D. DouerM. Tallman
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2005
TLDR
New therapeutic strategies evolving from its diverse biologic activities are discussed and arsenic trioxide may have antitumor activity in malignancies other than APL and that it may be used in combination with other agents to expand its potential use.

Complete remission after treatment of acute promyelocytic leukemia with arsenic trioxide.

TLDR
Low doses of arsenic trioxide can induce complete remissions in patients with APL who have relapsed and the clinical response is associated with incomplete cytodifferentiation and the induction of apoptosis with caspase activation in leukemic cells.

Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients.

TLDR
As2O3 treatment is an effective and relatively safe drug in APL patients refractory to ATRA and conventional chemotherapy, and Pharmacokinetic studies showed that after a peak level of 5.54 micromol/L, plasma arsenic was rapidly eliminated, and the continuous administration of As2O2 did not alter its pharmacokinetic behaviors.