In Vitro Inhibition of Piper nigrum and Piperine on Growth, Migration, and Invasion of PANC-1 Human Pancreatic Cancer Cells

Abstract

Several dietary and medicinal herbs have been shown to be effective in the treatment and prevention of cancer. Although Piper nigrum has been shown to have anti-cancer activities against various cancer cells, its anti-pancreatic cancer properties have not been reported. In the present study, P. nigrum extract (PNE) inhibited proliferation of PANC-1 human pancreatic cancer cells. Flow cytometry showed G0/G1 arrest caused by PNE in PANC-1 cells. In addition, Western blot analysis showed that PNE suppressed the protein levels of cell cycle regulators such as cyclin B1, cyclin D1, survivin, and Forkhead box M1 (FoxM1). These findings suggested that the inhibitory activity of PNE against the growth of PANC-1 cells was correlated with cell cycle arrest and repression of cell cycle regulators. Wound healing and trans-well assays showed that PNE suppressed migration and invasion of PANC-1 cells. Piperine, a major alkaloid of Piper nigrum, was identified as the main component of PNE by HPLC analysis. Piperine also attenuated the cell growth, migration, and invasion of PANC-1 cells, suggesting its contribution to the anti-pancreatic cancer effects of PNE. These results demonstrate that PNE and its major constituent, piperine, have anti-pancreatic cancer properties such as growth-inhibition, anti-migration, and anti-invasion of cancer cells.

Piperine: Chemistry and Biology

“…Rajarajan et al reported that the dietary piperine represented a potential candidate that could suppress obesity-associated breast cancer growth and metastasis by regulating the miR-181c-3p/PPARα Axis [ 33 ]. Furthermore, Jeong et al also found that piperine has anticancer properties such as growth inhibition, anti-migration, and anti-invasion of cancer cells [ 34 ]. In order to application of piperine derivatives as more potential anticancer drugs, structural modification has received much attention.…”

“…Molecular modeling revealed several interactions between derivates and acetylcholinesterase (AChE) substrate binding sites responsible for binding and inhibition [ 65 ]. As shown in Scheme 9 , twenty-two piperine derivates 2 , 52a – 52l , and 53a – 53i were synthesized by Zhong et al and evaluated for their anticancer properties [ 34 ]. As shown in Scheme 10 , a series of novel piperine derivates 56a – 56z , 56a’ – 56b’ , and 59a – 59b containing a linear bisamide were synthesized and evaluated for their insecticidal activities against P. xylostella [ 50 ].…”

“…The natural product piperine ( 1 ) and its derivates exhibit wide biological activity in the fields of medicine and agriculture. For example, piperine and its derivates have anticancer properties such as growth-inhibition, anti-migration, and anti-invasion of cancer cells by regulating the miR-181c-3p/PPARα Axis [ 32 ] and inhibiting thioredoxin reductase and carbonic anhydrase [ 34 , 35 ]. In addition, piperine can target endoplasmic reticulum autophagy (ER-phagy) in treating acute pancreatitis [ 42 ].…”

“…In particular, the long aliphatic chain esters or oxime esters, and a very crucial prerequisite is to retain the dioxymethylene ring [ 28 , 29 , 60 ]; (iii) introduction of the dienehydrazide groups can obtain potent insecticidal compounds against third-instar larval of C. pipiens [ 65 ]. The introduction of different substituted amides is beneficial for anticancer activity and can obtain a potential inhibitor against CYP2J2 [ 34 , 67 ]. Piperine derivates containing a linear bisamide exhibited significant insecticidal activity against P. xylostella , and they can be further studied as lead pesticidal agents [ 50 ].…”

GC-MS Analysis of the Active Compound in Ethanol Extracts of White Pepper (Piper nigrum L.) and Pharmacological Effects

“…Piperine is also known to be able to inhibit the quorum sensing system in the bacterium Chromobacterium violaceum CV026 with an effective dose of 30 mg/L so that it has potential as an antibacterial [31]. Piperine exhibits anti-proliferative, anti-migratory, and anti-invasive properties in human pancreatic cancer cells, PANC-1 [39]. Piperine has a hepatoprotective effect against Dgalactosamine (D-GalN)/lipopolysaccharideinduced damage to rat primary hepatocyte cells (LPS) [17].…”