Penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis

Pancreatic tumors exhibit enhanced autophagy as compared to any other cancer, making it resistant to chemotherapy. We evaluated the effect of penfluridol against pancreatic cancer. Penfluridol treatment induced apoptosis and inhibited the growth of Panc-1, BxPC-3 and AsPC-1, pancreatic cancer cells...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports Vol. 6; no. 1; p. 26165
Main Authors: Ranjan, Alok, Srivastava, Sanjay K.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 18.05.2016
Nature Publishing Group
Subjects:
13/109
13/2
14
14/5
38
631/67/1504/1713
64
64/60
692/4028/67/1059
96
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacology
Apoptosis
Apoptosis - drug effects
Autophagy
Autophagy - drug effects
Caspase
Caspase-3
Cell Line, Tumor
Chemotherapy
Chloroquine
Chloroquine - administration & dosage
Disease Models, Animal
Drug Therapy, Combination
Heterografts
Humanities and Social Sciences
Mice
multidisciplinary
Neoplasm Transplantation
Pancreatic cancer
Pancreatic Neoplasms - drug therapy
Pancreatic Neoplasms - pathology
Penfluridol - administration & dosage
Penfluridol - pharmacology
Phagocytosis
Phagosomes
Science
Treatment Outcome
Tumors
Xenografts
ISSN:2045-2322, 2045-2322
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Pancreatic tumors exhibit enhanced autophagy as compared to any other cancer, making it resistant to chemotherapy. We evaluated the effect of penfluridol against pancreatic cancer. Penfluridol treatment induced apoptosis and inhibited the growth of Panc-1, BxPC-3 and AsPC-1, pancreatic cancer cells with IC 50 ranging between 6–7 μM after 24 h of treatment. Significant autophagy was induced by penfluridol treatment in pancreatic cancer cells. Punctate LC3B and autophagosomes staining confirmed autophagy. Inhibiting autophagy by chloroquine, bafilomycin, 3-methyladenine or LC3BsiRNA, significantly blocked penfluridol-induced apoptosis, suggesting that autophagy lead to apoptosis in our model. Penfluridol treatment suppressed the growth of BxPC-3 tumor xenografts by 48% as compared to 17% when treated in combination with chloroquine. Similarly, penfluridol suppressed the growth of AsPC-1 tumors by 40% versus 16% when given in combination with chloroquine. TUNEL staining and caspase-3 cleavage revealed less apoptosis in the tumors from mice treated with penfluridol and chloroquine as compared to penfluridol alone. Penfluridol treatment also suppressed the growth of orthotopically implanted Panc-1 tumors by 80% by inducing autophagy-mediated apoptosis in the tumors. These studies established that penfluridol inhibits pancreatic tumor growth by autophagy-mediated apoptosis. Since penfluridol is already in clinic, positive findings from our study will accelerate its clinical development.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:2045-2322
2045-2322
DOI:10.1038/srep26165