HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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.

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.
AuthorsBilal Bin Hafeez, Mohammad Sarwar Jamal, Joseph W Fischer, Ala Mustafa, Ajit Kumar Verma
JournalInternational journal of cancer (Int J Cancer) Vol. 131 Issue 9 Pg. 2175-86 (Nov 01 2012) ISSN: 1097-0215 [Electronic] United States
PMID22322442 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 UICC.
Chemical References
  • Antineoplastic Agents, Phytogenic
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Matrix Metalloproteinase Inhibitors
  • NF-kappa B
  • Naphthoquinones
  • Plant Extracts
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Survivin
  • Cyclin D1
  • ErbB Receptors
  • plumbagin
Topics
  • Animals
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Apoptosis (drug effects)
  • Cell Line, Tumor (drug effects)
  • Cell Proliferation (drug effects)
  • Cyclin D1 (antagonists & inhibitors)
  • ErbB Receptors (metabolism)
  • Humans
  • Inhibitor of Apoptosis Proteins (antagonists & inhibitors)
  • Male
  • Matrix Metalloproteinase Inhibitors
  • Mice
  • Mice, SCID
  • NF-kappa B (metabolism)
  • Naphthoquinones (pharmacology)
  • Pancreatic Neoplasms (drug therapy, pathology)
  • Phosphorylation
  • Plant Extracts (pharmacology)
  • STAT3 Transcription Factor (metabolism)
  • Signal Transduction (drug effects)
  • Survivin

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: