Synergy of theophylline reduces necrotic effect of berberine, induces cell cycle arrest and PARP, HMGB1, Bcl-2 family mediated apoptosis in MDA-MB-231 breast cancer cells

Hashemi-Niasari, F. and Rabbani-Chadegani, A. and Razmi, M. and Fallah, S. (2018) Synergy of theophylline reduces necrotic effect of berberine, induces cell cycle arrest and PARP, HMGB1, Bcl-2 family mediated apoptosis in MDA-MB-231 breast cancer cells. Biomedicine and Pharmacotherapy, 106. pp. 858-867.

Full text not available from this repository.
Official URL: https://www.scopus.com/inward/record.uri?eid=2-s2....

Abstract

Berberine, is a plant alkaloid, proved to have anticancer effect on various cancers. Theophylline (TH), a natural product, is widely used in the treatment of respiratory difficulties. The present study designed to elucidate the effects of theophylline and berberine combination on breast cancer cells cytotoxicity, gene expression and cell cycle. MTT assay revealed that berberine inhibited MDA-MB-231 breast cancer cells viability in a time and dose dependent manner (IC50 of 100 μM) but theophylline had no considerably effect on the cells. Combined treatment of berberine and theophylline showed a synergistic anti-proliferation effect, IC50 of berberine reduced to 50 μM and the cells were arrested at G2/M phase. Combined treatment of Berberine and theophylline reduced extracellular level of HMGB1 and down regulated HMGB1 and MMP-9 mRNA expression. The results of flow cytometry using annexin/PI staining of the cells, HMGB1 release, and poly ADP ribose polymerase cleavage demonstrated that theophylline attenuated necrotic effect of berberine and increased the level of apoptotic cell death. Enhancement of Bax content detected by ELISA and upregulation of Bax mRNA expression, down-regulation of Bcl-2 expression and increase of anion superoxide production confirmed induction of apoptosis via intrinsic apoptotic pathway. Replacement of theophylline with exogenous cyclic AMP in combination treatment represented similar effect on berberine cytotoxicity. From the results it is concluded that synergistic anticancer effect of theophylline and berberine suggests that combination of these two drugs may be an effective therapeutic agent against breast cancer cell. © 2018 Elsevier Masson SAS

Item Type: Article
Additional Information: cited By 0
Uncontrolled Keywords: berberine; cyclic AMP; gelatinase B; high mobility group B1 protein; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; protein Bax; protein bcl 2; theophylline, antiproliferative activity; apoptosis; Article; cell cycle arrest; cell death; cell growth; cell proliferation; cell viability; colony formation; controlled study; down regulation; drug cytotoxicity; drug design; drug potentiation; enzyme linked immunosorbent assay; flow cytometry; G2 phase cell cycle checkpoint; gene expression; human; human cell; IC50; immunoblotting; MDA-MB-231 cell line; MTT assay; necrosis; priority journal; real time polymerase chain reaction; trypan blue assay; upregulation; Western blotting
Subjects: WP Gynecology
QV Pharmacology
Depositing User: eprints admin
Date Deposited: 25 Dec 2018 12:43
Last Modified: 25 Dec 2018 12:43
URI: http://eprints.iums.ac.ir/id/eprint/6212

Actions (login required)

View Item View Item