Nayak, Anmada ; Satapathy, Shakti Ranjan ; Das, Dipon ; Siddharth, Sumit ; Tripathi, Neha ; Bharatam, Prasad V. ; Kundu, ChanakyaNath (2016) Nanoquinacrine induced apoptosis in cervical cancer stem cells through the inhibition of hedgehog-GLI1 cascade: Role of GLI-1 Scientific Reports, 6 (1). ISSN 2045-2322
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Official URL: http://doi.org/10.1038/srep20600
Related URL: http://dx.doi.org/10.1038/srep20600
Abstract
To improve the pharmacokinetics and to study the anti-cervical cancer and anti-stem cells (CSCs) mechanism of Quinacrine (QC), a spherical nano particle of QC (i.e. NQC) was prepared and characterized. QC and NQC showed higher cytotoxicity in multiple cancer cells than the normal epithelial cells. NQC exhibited more toxicity in cervical cancer cells and its CSCs than QC. A dose-dependent decreased expression of Hedgehog-GLI (HH-GLI) components were noted in NQC treated HeLa cells and its CSCs. NQC increased the expressions of negatively regulated HH-GLI components (GSK3β, PTEN) and caused apoptosis in CSCs. Reduction of GLI1 at mRNA and promoter level were noted after NQC exposure. The expressions of HH-GLI components, GLI1 promoter activity and apoptosis were unaltered in NQC treated GLI1-knockdown cells. In silico, cell based and in vitro reconstitution assay revealed that NQC inhibit HH-GLI cascade by binding to the consensus sequence (5'GACCACCCA3') of GLI1 in GLI-DNA complex through destabilizing DNA-GLI1 complex. NQC reduced the tumors size and proliferation marker Ki-67 in an in vivo xenograft mice model. Thus, NQC induced apoptosis in cancers through inhibition of HH-GLI cascade by GLI1. Detail interaction of QC-DNA-GLI complex can pave path for anticancer drug design.
Item Type: | Article |
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Source: | Copyright of this article belongs to FOIA Privacy. |
ID Code: | 116385 |
Deposited On: | 12 Apr 2021 09:29 |
Last Modified: | 12 Apr 2021 09:29 |
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