Quinacrine inhibits GSTA1 activity and induces apoptosis through G 1 /S arrest and generation of ROS in human non-small cell lung cancer cell lines

Makhan Kumar; Ansie Martin; Snehal Nirgude; Bibha Chaudhary; Sukanta Mondal; Angshuman Sarkar

doi:10.18632/oncotarget.27558

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This article has been corrected. Correction in: Oncotarget. 2020; 11:4364-4365.

Quinacrine inhibits GSTA1 activity and induces apoptosis through G₁/S arrest and generation of ROS in human non-small cell lung cancer cell lines

Makhan Kumar, Ansie Martin, Snehal Nirgude, Bibha Chaudhary, Sukanta Mondal and Angshuman Sarkar _

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Abstract

Makhan Kumar1, Ansie Martin1^,4, Snehal Nirgude2^,3, Bibha Chaudhary2, Sukanta Mondal1 and Angshuman Sarkar1

1 CMBL, Department of Biological Sciences, CMBL, BITS Pilani K K Birla Goa Campus, Zuarinagar, Goa 40372, India

2 Institute of Bioinformatics and Applied Biotechnology (IBAB), Bangalore, Electronics City Phase 1, Bengaluru, Karnataka 560100, India

3 Manipal Academy of Higher Education, Manipal, Karnataka 576104, India

4 Present Address: UMR 1236, Faculty of Medicine, Rennes 35043, France

Correspondence to:

Angshuman Sarkar,

email:

[email protected]

Keywords: quinacrine; NSCLC; RhoGTPases; apoptosis; cell cycle

Received: August 06, 2019 Accepted: December 02, 2019 Published: May 05, 2020

ABSTRACT

Background: Quinacrine (QC) is popular for its anti-malarial activity. It has been reported exhibiting anti-cancerous properties by suppressing nuclear factor-κB and activating p53 signaling; however, its effect on cellular pathways in human non-small cell lung cancer (NSCLC) has not been studied.

Materials and Methods: Binding of QC with GSTA1 was studied computationally as well as through GST activity assay kit. Cell viability, cell cycle and mitochondrial membrane potential activity were studied using flow cytometry. RT-PCR and western blot were carried out to understand the involvement of various genes at their mRNA as well as protein level.

Results: QC inhibited the activity of GSTA1 approximately by 40–45% which inhibits cell survival and promotes apoptosis. QC reduced viability of NSCLC cells in a dose-dependent manner. It also causes nuclear fragmentation, G₁/S arrest of cell cycle and ROS generation; which along with disruption of mitochondrial membrane potential activity leads to apoptotic fate.

Conclusions: Results revealed, QC has promising anti-cancer potential against NSCLC cells via inhibition of GSTA1, induction of G₁/S arrest and ROS mediated apoptotic signaling.

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Quinacrine inhibits GSTA1 activity and induces apoptosis through G1/S arrest and generation of ROS in human non-small cell lung cancer cell lines

Abstract

Quinacrine inhibits GSTA1 activity and induces apoptosis through G₁/S arrest and generation of ROS in human non-small cell lung cancer cell lines