Piperine functions as a tumor suppressor for human ovarian tumor growth via activation of JNK/p38 MAPK-mediated intrinsic apoptotic pathway

Biosci Rep. 2018 May 31;38(3):BSR20180503. doi: 10.1042/BSR20180503. Print 2018 Jun 29.


Piperine, a kind of natural alkaloid found in the fruit of black (Piper nigrum Linn) and long (Piper longum Linn), has shown antitumor activities toward various cancer cell lines. However, the antitumor effects of Piperine on ovarian cancer and the underlying mechanism are not fully elucidated. Our result showed that Piperine reduced the cell viability of A2780 cells in a concentration and time-dependent manner, but has not any effect on normal ovarian cells. Flow cytometric analysis revealed that Piperine suppressed cells proliferation via induction of apoptosis, which was followed by release of mitochondrial cytochrome c to cytosol, activation of caspase-3 and -9, as well as cleaved PARP. Moreover, Western blot results confirmed that Piperine (8, 16, and 20 μM) decreased phosphorylation of JNK and p38 MAPK in A2780 cells. In addition, caspase-3 inhibitor (Z-DEVD-FMK), caspase-9 inhibitor (Z-LEDH-FMK), JNK-inhibitor (SP600125), or p38 MAPK inhibitor (SB203580) could abate the apoptosis induced by Piperine (20 μM) treatment, while caspase-8 inhibitor (Z-IETD- FMK) exhibited no inhibitory effect on the induction of apoptosis in A2780 cells. These results provide the first evidence for the anticancer potential of Piperine in ovarian cancer cells, partially via JNK/p38 MAPK-mediated intrinsic apoptotic pathway.

Keywords: Apoptosis; Caspase; JNK; Mitochondria; Piperine; p38 MARK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Anthracenes / pharmacology
  • Apoptosis / drug effects
  • Benzodioxoles / pharmacology*
  • Caspase 3 / drug effects
  • Caspase 3 / genetics
  • Caspase 9 / drug effects
  • Caspase 9 / genetics
  • Caspase Inhibitors / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Female
  • Humans
  • Imidazoles / pharmacology
  • MAP Kinase Kinase 4 / genetics*
  • Oligopeptides / pharmacology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides / pharmacology*
  • Pyridines / pharmacology
  • Tumor Suppressor Proteins / genetics
  • p38 Mitogen-Activated Protein Kinases / genetics*


  • Alkaloids
  • Anthracenes
  • Benzodioxoles
  • Caspase Inhibitors
  • Imidazoles
  • Oligopeptides
  • Piperidines
  • Polyunsaturated Alkamides
  • Pyridines
  • Tumor Suppressor Proteins
  • benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone
  • benzyloxycarbonyl-leucyl-glutamyl-histidyl-aspartic acid fluoromethyl ketone
  • pyrazolanthrone
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Caspase 3
  • Caspase 9
  • SB 203580
  • piperine