Palmatine suppresses glutamine-mediated interaction between pancreatic cancer and stellate cells through simultaneous inhibition of survivin and COL1A1

Divya Chakravarthy, Amanda R. Muñoz, Angel Su, Rosa F. Hwang, Brian R. Keppler, Daniel E. Chan, Glenn A Halff, Rita Ghosh, Addanki P Kumar

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Reciprocal interaction between pancreatic stellate cells (PSCs) and cancer cells (PCCs) in the tumor microenvironment (TME) promotes tumor cell survival and progression to lethal, therapeutically resistant pancreatic cancer. The goal of this study was to test the ability of Palmatine (PMT) to disrupt this reciprocal interaction in vitro and examine the underlying mechanism of interaction. We show that PSCs secrete glutamine into the extracellular environment under nutrient deprivation. PMT suppresses glutamine-mediated changes in GLI signaling in PCCs resulting in the inhibition of growth and migration while inducing apoptosis by inhibition of survivin. PMT-mediated inhibition of (glioma-associated oncogene 1) GLI activity in stellate cells leads to suppression (collagen type 1 alpha 1) COL1A1 activation. Remarkably, PMT potentiated gemcitabine's growth inhibitory activity in PSCs, PCCs and inherently gemcitabine-resistant pancreatic cancer cells. This is the first study that shows the ability of PMT to inhibit growth of PSCs and PCCs either alone or in combination with gemcitabine. These studies warrant additional investigations using preclinical models to develop PMT as an agent for clinical management of pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)103-115
Number of pages13
JournalCancer Letters
Volume419
DOIs
StatePublished - Apr 10 2018

Fingerprint

Pancreatic Stellate Cells
gemcitabine
Glutamine
Pancreatic Neoplasms
Neoplasms
Growth
Tumor Microenvironment
Collagen Type I
Oncogenes
Glioma
palmatine
Cell Survival
Apoptosis
Food

Keywords

  • Desmoplasia
  • GLI signaling
  • glutamine
  • Palmatine
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Palmatine suppresses glutamine-mediated interaction between pancreatic cancer and stellate cells through simultaneous inhibition of survivin and COL1A1. / Chakravarthy, Divya; Muñoz, Amanda R.; Su, Angel; Hwang, Rosa F.; Keppler, Brian R.; Chan, Daniel E.; Halff, Glenn A; Ghosh, Rita; Kumar, Addanki P.

In: Cancer Letters, Vol. 419, 10.04.2018, p. 103-115.

Research output: Contribution to journalArticle

Chakravarthy, Divya ; Muñoz, Amanda R. ; Su, Angel ; Hwang, Rosa F. ; Keppler, Brian R. ; Chan, Daniel E. ; Halff, Glenn A ; Ghosh, Rita ; Kumar, Addanki P. / Palmatine suppresses glutamine-mediated interaction between pancreatic cancer and stellate cells through simultaneous inhibition of survivin and COL1A1. In: Cancer Letters. 2018 ; Vol. 419. pp. 103-115.
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