Anticancer and Multidrug Resistance-reversal Effects of Solanidine Analogs Synthetized from Pregnadienolone Acetate

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2014 Feb 20

PMID 24549231

Citations 9

Authors

Istvan Zupko

Judit Molnar

Borbala Rethy

Renata Minorics

Eva Frank

Janos Wolfling

Joseph Molnar

Imre Ocsovszki

Zeki Topcu

Tamas Bito

Laszlo G Puskas

Affiliations

Soon will be listed here.

Abstract

A set of solanidine analogs with antiproliferative properties were recently synthetized from pregnadienolone acetate, which occurs in Nature. The aim of the present study was an in vitro characterization of their antiproliferative action and an investigation of their multidrug resistance-reversal activity on cancer cells. Six of the compounds elicited the accumulation of a hypodiploid population of HeLa cells, indicating their apoptosis-inducing character, and another one caused cell cycle arrest at the G2/M phase. The most effective agents inhibited the activity of topoisomerase I, as evidenced by plasmid supercoil relaxation assays. One of the most potent analogs down-regulated the expression of cell-cycle related genes at the mRNA level, including tumor necrosis factor alpha and S-phase kinase-associated protein 2, and induced growth arrest and DNA damage protein 45 alpha. Some of the investigated compounds inhibited the ABCB1 transporter and caused rhodamine-123 accumulation in murine lymphoma cells transfected by human MDR1 gene, expressing the efflux pump (L5178). One of the most active agents in this aspect potentiated the antiproliferative action of doxorubicin without substantial intrinsic cytostatic capacity. The current results indicate that the modified solanidine skeleton is a suitable substrate for the rational design and synthesis of further innovative drug candidates with anticancer activities.

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