Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Cyclopentadione-aniline conjugate suppresses proliferation and induces apoptosis in liver cancer cells via up-regulation of p38 phosphorylation

For correspondence:-

Accepted: 26 February 2019 Published: 31 March 2019

Citation: Cyclopentadione-aniline conjugate suppresses proliferation and induces apoptosis in liver cancer cells via up-regulation of p38 phosphorylation. Trop J Pharm Res 2019; 18(3):505-511 doi: 10.4314/tjpr.v18i3.9

© 2019 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the effect of cyclopentadione-aniline conjugate (CAC) on proliferation of liver cancer cells.

Methods: MTT assay and flow cytometry were used for the determination of the effect of CAC on cell proliferation and apoptosis. Western blotting was used to measure the influence of CAC on the expressions of various proteins, while Matrigel-coated Transwell assay was used for assessment of cell invasion.

Results: CAC inhibited proliferation of liver cancer cells in a concentration-dependent manner. The degree of proliferation of HepG2 cells was 98, 89, 76, 66, 51, 42 or 36 %, on treatment with 0.25, 0.5, 1.0, 1.5, 2.0, 2.5 or 3.0 µM CAC, respectively. In H4TG cells, treatment with 0.25, 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 µM CAC decreased proliferation of cells to 99, 91, 79, 70, 54, 46 and 40 %, respectively. Apoptosis was induced in 34.56, 37.37 and 52.98 % cells, on treatment with 2.0, 2.5 and 3.0 µM CAC, respectively. The invasive potential of HepG2 cells was significantly decreased by CAC (p < 0.05). Marked decreases were observed in Bcl-2, MMP-2, MMP-9, c-ERK1/2 and phospho-Akt levels in CAC-treated HepG2 cells. CAC treatment markedly upregulated Bax and phospho ERK1/2, but significantly downregulated phospho PI3K, phospho mTOR and phospho Akt in HepG2 cells (p < 0.05). However, the level of phospho p38 was decreased in CAC-treated cells.

Conclusion: These results demonstrate that CAC inhibits proliferation of liver cancer cells via apoptosis induction. Thus, CAC can potentially be used for the treatment of liver cancer in humans.

Keywords: Phosphoinositide 3 kinase, Phospho p38, Apoptosis, Mitochondria, Collagen