Next Article in Journal
Characterizing the Structural and Functional Properties of Soybean Protein Extracted from Full-Fat Soybean Flakes after Low-Temperature Dry Extrusion
Previous Article in Journal
Vibrational Spectroscopy for Cocrystals Screening. A Comparative Study
Article Menu
Issue 12 (December) cover image

Export Article

Open AccessArticle

A Novel Synthetic Dihydroindeno[1,2-b] Indole Derivative (LS-2-3j) Reverses ABCB1- and ABCG2-Mediated Multidrug Resistance in Cancer Cells

1
School of Ocean, Shandong University, Weihai 264209, China
2
Department of Biomedical Engineering, Faculty of Electronic Information and Electrical Engineering, Dalian University of Technology, Dalian 116024, China
3
Research Center for the Control Engineering of Translational Precision Medicine, Dalian University of Technology, Dalian 116024, China
4
The Key Laboratory of Chemistry for Natural Product of Guizhou Province, Chinese Academy of Science, Guiyang 550002, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this study.
Molecules 2018, 23(12), 3264; https://doi.org/10.3390/molecules23123264
Received: 10 November 2018 / Revised: 5 December 2018 / Accepted: 7 December 2018 / Published: 10 December 2018
  |  
PDF [7764 KB, uploaded 10 December 2018]
  |     |  

Abstract

10-oxo-5-(3-(pyrrolidin-1-yl) propyl)-5,10-dihydroindeno [1,2-b] indol-9-yl propionate (LS-2-3j) is a new chemically synthesized indole compound and some related analogues are known to be inhibitors (such as alectinib and Ko143) of ATP-binding cassette (ABC) transporters, especially the ABC transporter subfamily B member 1 (ABCB1) and the ABC transporter subfamily G member 2 (ABCG2). This study aimed to evaluate the multidrug resistance (MDR) reversal effects and associated mechanisms of LS-2-3j in drug-resistant cancer cells. The inhibition of cell proliferation in tested agents was evaluated by the 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay. Accumulation or efflux of chemotherapy drugs was analyzed by flow cytometry. The ATPase activity was measured using an ATPase activity assay kit. The mRNA transcripts and protein expression levels were detected by real-time PCR and Western blot, respectively. In this connection, LS-2-3j significantly enhanced the activity of chemotherapeutic drugs in MDR cells and could significantly increase the intracellular accumulation of doxorubicin (DOX) and mitoxantrone (MITX) by inhibiting the function of the efflux pumps in ABCB1- or ABCG2-overexpressing cells. Furthermore, reduced ATPase activity, mRNA transcription, and protein expression levels of ABCB1 and ABCG2 were observed in a concentration dependent manner in MDR cancer cells. View Full-Text
Keywords: indole derivative; multidrug resistance; K562/A02 cell line; MCF-7/ABCG2 cell line; ABCB1; ABCG2 indole derivative; multidrug resistance; K562/A02 cell line; MCF-7/ABCG2 cell line; ABCB1; ABCG2
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Guo, C.; Liu, F.; Qi, J.; Ma, J.; Lin, S.; Zhang, C.; Zhang, Q.; Zhang, H.; Lu, R.; Li, X. A Novel Synthetic Dihydroindeno[1,2-b] Indole Derivative (LS-2-3j) Reverses ABCB1- and ABCG2-Mediated Multidrug Resistance in Cancer Cells. Molecules 2018, 23, 3264.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top