Pyrvinium Targets the Unfolded Protein Response to Hypoglycemia and Its Anti-Tumor Activity Is Enhanced by Combination Therapy
2008

Pyrvinium's Role in Cancer Treatment

Sample size: 10 publication 10 minutes Evidence: moderate

Author Information

Author(s): Yu De-Hua, Macdonald James, Liu Guohong, Lee Amy S., Ly Mimi, Davis Timothy, Ke Ning, Zhou Demin, Wong-Staal Flossie, Li Qi-Xiang

Primary Institution: iTherX Pharmaceuticals, Inc.

Hypothesis

Can pyrvinium pamoate enhance anti-tumor activity by targeting the unfolded protein response during hypoglycemia?

Conclusion

Pyrvinium pamoate shows limited anti-tumor activity alone but significantly enhances the efficacy of doxorubicin in cancer treatment.

Supporting Evidence

  • Pyrvinium preferentially inhibits anchorage-independent growth of cancer cells.
  • It suppresses the transcriptional activation of GRP78 and GRP94 under glucose deprivation.
  • Combination therapy with doxorubicin showed significantly enhanced efficacy in vivo.
  • Over-expression of GRP78 protects cells from pyrvinium-induced cell death.

Takeaway

Pyrvinium is a medicine that helps fight cancer by making cancer cells more sensitive to low sugar levels, especially when used with another drug called doxorubicin.

Methodology

The study involved in vitro assays to test the effects of pyrvinium on cancer cell growth under glucose deprivation and in vivo xenograft models to assess anti-tumor activity.

Potential Biases

Potential bias due to funding from iTherX Pharmaceuticals, which may influence study outcomes.

Limitations

The anti-tumor activity of pyrvinium alone was marginal, and the study was limited to specific cancer models.

Participant Demographics

The study involved various cancer cell lines and xenograft models, but specific demographics of human participants were not provided.

Statistical Information

P-Value

0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0003951

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