Plumbagin, a plant derived natural agent inhibits the growth of pancreatic cancer cells in in vitro and in vivo via targeting EGFR, Stat3 and NF-κB signaling pathways

Bilal Bin Hafeez, Mohammad Sarwar Jamal, Joseph W. Fischer, Ala Mustafa, Ajit Kumar Verma

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Pancreatic cancer (PC) is the most aggressive malignant disease, ranks as the fourth most leading cause of cancer-related death among men and women in the United States. We present here that plumbagin (PL), a quinoid constituent isolated from the roots of the medicinal plant Plumbago zeylanica L, inhibits the growth of PC cells both in vitro and in vivo model systems. PL treatment induces apoptosis and inhibits cell viability of PC cells (PANC1, BxPC3 and ASPC1). In addition, i.p. administration of PL (2 mg/kg body weight, 5 days a week) in severe combined immunodeficiency (SCID) mice beginning 3 days after ectopic implantation of PANC1 cells resulted in a significant (P < 0.01) inhibition of both tumor weight and volume. PL treatment inhibited (1) constitutive expression of epidermal growth factor receptor (EGFR), pStat3Tyr705 and pStat3Ser727, (2) DNA binding of Stat3 and (3) physical interaction of EGFR with Stat3, in both cultured PANC1 cells and their xenograft tumors. PL treatment also inhibited phosphorylation and DNA-binding activity of NF-κB in both cultured PC cells (PANC1 and ASPC1) and in PANC1 cells xenograft tumors. Downstream target genes (cyclin D1, MMP9 and Survivin) of Stat3 and NF-κB were similarly inhibited. These results suggest that PL may be used as a novel therapeutic agent against human PC. Published 2012 Wiley-Liss, Inc. This article is a US Government work, and, as such, is in the public domain in the United States of America.

Original languageEnglish (US)
Pages (from-to)2175-2186
Number of pages12
JournalInternational Journal of Cancer
Volume131
Issue number9
DOIs
StatePublished - Nov 1 2012

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Pancreatic Neoplasms
Epidermal Growth Factor Receptor
Growth
Tumor Burden
Heterografts
Plumbaginaceae
bcl-1 Genes
Severe Combined Immunodeficiency
Neoplasms
Public Sector
DNA
Therapeutics
Medicinal Plants
plumbagin
In Vitro Techniques
Cultured Cells
Cell Survival
Body Weight
Phosphorylation
Apoptosis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Plumbagin, a plant derived natural agent inhibits the growth of pancreatic cancer cells in in vitro and in vivo via targeting EGFR, Stat3 and NF-κB signaling pathways. / Hafeez, Bilal Bin; Jamal, Mohammad Sarwar; Fischer, Joseph W.; Mustafa, Ala; Verma, Ajit Kumar.

In: International Journal of Cancer, Vol. 131, No. 9, 01.11.2012, p. 2175-2186.

Research output: Contribution to journalArticle

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