title: Antiproliferative effects of curcumin analog L49H37 in pancreatic stellate cells: a comparative study.
abstract: BACKGROUND
  Pancreatic cancer is a devastating disease with poor prognosis. It is characterized by a pronounced stromal reaction, which resists chemotherapeutics and effective tumor treatment. Pancreatic stellate cells (PSCs) are mainly responsible for this stromal reaction. Moreover, the cancer and stromal interaction seems to promote tumor proliferation. In this study, L49H37, a newly synthesized curcumin analog, was used as intervention to target the stromal compartment of pancreatic cancer.
  
  
  METHODS
  In vitrocultures of human PSCs were exposed to curcumin and L49H37. Cell viability as well as growth promoting and survival signaling pathways were monitored by MTT, flow cytometry and western blotting.
  
  
  RESULTS
  Curcumin and L49H37 effectively inhibited proliferation and induced apoptosis in PSCs. L49H37 was found to be more potent at a lower concentration than curcumin in the induction of apoptosis, as evidenced by cleaved poly (ADP-ribose) polymerase (PARP). The cells were retained in the G0/G1 phase of the cell cycle through the downregulation of p21WAF1/Cip1. L49H37 significantly decreased the phosphorylation of extracellular signal regulated kinase ½ (ERK½).
  
  
  CONCLUSIONS
  The results indicate that curcumin analog L49H37 exhibits more potent inhibitory effects than curcumin itself at a lower concentration, which suggests that it may have a potential for further evaluation of its use against pancreatic adenocarcinoma, either as a single agent but, more probable, as part of a combination regimen.
authors.affiliation: Department of Surgery, Clinical Sciences, Lund University, Lund, Skåne, Sweden (Chinmay Gundewar, Daniel Ansari, Ann H. Rosendahl, Roland Andersson).
authors.forename: Chinmay
authors.initials: C
authors.lastname: Gundewar
authors.affiliation: Department of Surgery, Clinical Sciences, Lund University, Lund, Skåne, Sweden (Chinmay Gundewar, Daniel Ansari, Ann H. Rosendahl, Roland Andersson) ; Department of Surgery, Skåne University Hospital Lund, Lund, Skåne, Sweden (Daniel Ansari, Roland Andersson).
authors.forename: Daniel
authors.initials: D
authors.lastname: Ansari
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China (Longguang Tang, Yi Wang, Guang Liang).
authors.forename: Longguang
authors.initials: L
authors.lastname: Tang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China (Longguang Tang, Yi Wang, Guang Liang).
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China (Longguang Tang, Yi Wang, Guang Liang).
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
authors.affiliation: Department of Surgery, Clinical Sciences, Lund University, Lund, Skåne, Sweden (Chinmay Gundewar, Daniel Ansari, Ann H. Rosendahl, Roland Andersson) ; Department of Oncology, Clinical Sciences, Skåne University Hospital Lund, Lund University, Lund, Skåne, Sweden (Ann H. Rosendahl).
authors.forename: Ann H
authors.initials: AH
authors.lastname: Rosendahl
authors.affiliation: Children's Renal Unit and Academic Renal Unit, University of Bristol, Learning and Research Building, Southmead Hospital, Bristol, United Kingdom (Moin A. Saleem).
authors.forename: Moin A
authors.initials: MA
authors.lastname: Saleem
authors.affiliation: Department of Surgery, Clinical Sciences, Lund University, Lund, Skåne, Sweden (Chinmay Gundewar, Daniel Ansari, Ann H. Rosendahl, Roland Andersson) ; Department of Oncology, Clinical Sciences, Skåne University Hospital Lund, Lund University, Lund, Skåne, Sweden (Ann H. Rosendahl).
authors.forename: Roland
authors.initials: R
authors.lastname: Andersson
keywords: Pancreatic cancer; cleaved PARP; p21WAF1/Cip1; stroma