Bioavailability and Efficacy of a Gap Junction Enhancer (PQ7) in a Mouse Mammary Tumor Model

Stephanie N. Shishido, Keshar Prasain, Amanda P. Beck, Thi D T Nguyen, Duy H. Hua, Thu Annelise Nguyen

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The loss of gap junctional intercellular communication is characteristic of neoplastic cells, suggesting that the restoration with a gap junction enhancer may be a new therapeutic treatment option with less detrimental effects than traditional antineoplastic drugs. A gap junction enhancer, 6-methoxy-8-[(2-furanylmethyl) amino]-4-methyl-5-(3-trifluoromethylphenyloxy) quinoline (PQ7), on the normal tissue was evaluated in healthy C57BL/6J mice in a systemic drug distribution study. Immunoblot analysis of the vital organs indicates a reduction in Cx43 expression in PQ7-treated animals with no observable change in morphology. Next the transgenic strain FVB/N-Tg(MMTV-PyVT) 634Mul/J (also known as PyVT) was used as a spontaneous mammary tumor mouse model to determine the biological and histological effects of PQ7 on tumorigenesis and metastasis at three stages of development: Pre tumor, Early tumor, and Late tumor formation. PQ7 was assessed to have a low toxicity through intraperitoneal administration, with the majority of the compound being detected in the heart, liver, and lungs six hours post injection. The treatment of tumor bearing animals with PQ7 had a 98% reduction in tumor growth, while also decreasing the total tumor burden compared to control mice during the Pre stage of development. PQ7 treatment increased Cx43 expression in the neoplastic tissue during Pre-tumor formation; however, this effect was not observed in Late stage tumor formation. This study shows that the gap junction enhancer, PQ7, has low toxicity to normal tissue in healthy C57BL/6J mice, while having clinical efficacy in the treatment of spontaneous mammary tumors of PyVT mice. Additionally, gap junctional intercellular communication and neoplastic cellular growth are shown to be inversely related, while treatment with PQ7 inhibits tumor growth through targeting gap junction expression.

Original languageEnglish (US)
Article numbere67174
JournalPLoS One
Volume8
Issue number6
DOIs
StatePublished - Jun 12 2013
Externally publishedYes

Fingerprint

gap junctions
mammary neoplasms (animal)
Gap Junctions
Biological Availability
bioavailability
Tumors
Breast Neoplasms
neoplasms
mice
Neoplasms
Connexin 43
cell communication
Inbred C57BL Mouse
Therapeutics
Growth
Tissue
Toxicity
toxicity
Animals
quinoline

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bioavailability and Efficacy of a Gap Junction Enhancer (PQ7) in a Mouse Mammary Tumor Model. / Shishido, Stephanie N.; Prasain, Keshar; Beck, Amanda P.; Nguyen, Thi D T; Hua, Duy H.; Nguyen, Thu Annelise.

In: PLoS One, Vol. 8, No. 6, e67174, 12.06.2013.

Research output: Contribution to journalArticle

Shishido, Stephanie N. ; Prasain, Keshar ; Beck, Amanda P. ; Nguyen, Thi D T ; Hua, Duy H. ; Nguyen, Thu Annelise. / Bioavailability and Efficacy of a Gap Junction Enhancer (PQ7) in a Mouse Mammary Tumor Model. In: PLoS One. 2013 ; Vol. 8, No. 6.
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