Comparative and Mechanistic Study on the Anticancer Activity of Quinacrine-Based Silver and Gold Hybrid Nanoparticles in Head and Neck Cancer
Authors: Birendra Kumar Bindhani
Deepika Nayak
Chanakya Nath Kundu
Krushna Chandra Hembram
Sefinew Molla
Chinmayee Sethy
Rajalaxmi Pradhan
Subhajit Chatterjee
Journal: Molecular Pharmaceutics (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: apoptosis; hybrid nanoparticles; oral cancer; quinacrine; re-replication

Abstract:  Using oral cancer cells ( in vitro) and in vivo xenograft mice model, we have systematically studied the detailed mechanism of anticancer activity of quinacrine-based hybrid silver (QAgNP) and gold (QAuNP) nanoparticles (NPs) and compared their efficacies. Both the NPs showed characteristic anti-cell proliferation profile in various cancer cells with minimally affecting the normal nontransformed breast epithelial MCF-10A cells. The IC50 values of QAuNP in various cancer cells were less compared to QAgNP and also found to be the lowest (0.5 μg/mL) in SCC-9 oral cancer cells. Although both NPs caused apoptosis by increased DNA damage, arresting at S phase and simultaneously inhibiting the DNA repair activity in cells, efficacy of QAuNP was better than that of QAgNP. NPs intercalated with DNA and inhibited the topoisomerase activity in cells. Alteration in expression of cell cycle regulatory (cyclins B1, E1, A2, etc.) and replication-related (MRE11, RPA, RFC, etc.) proteins were also observed after NP exposure to the cells. Accumulation of cells resulted in extended G/M phase after prolonged exposure of QAuNP in SCC-9 cells. Interestingly, depletion of geminin and increase of Cdt-1 along with CDC-6 suggest the formation of re-replication. Recovery of body weight and reduction in tumor volume were found in NP-treated xenograft mice. Induction of Bax/Bcl-xL, PARP-1 cleavage, p53, and p21 were noted in NP-treated xenograft mice tissue samples. Thus, data suggest that NP inhibits topoisomerase activity, thereby inhibiting DNA replication and inducing re-replication, which causes S-phase arrest, DNA damage, and finally apoptosis of the oral cancer cells. Also, it was found that anticancer activity of QAuNP is better than that of QAgNP. 

Retracted: No

PubPeer comments:
 Figure 7. * Blue boxes: A possible overlap between  Brest fat pad RPA QAgNP and  Brest fat pad RPA QAuNP. * Green boxes: A possible overlap between  Liver Topo IIa PBS and  Liver RPA QAgNP. * Teal boxes: A possible overlap between  Liver Topo IIa QAuNP and  Liver RPA Tumor. ![file] , 
 An error was noticed in Figure 7d (page no. 3019) of this original article after publication. Three microscopy images of the IHC experiment were noticed to be similar. This happened while processing the images during the revision. So, we have replaced this figure with the new Figure 7d as follows for the awareness of the readers. However, this replacement does not affect the results, scientific content, or conclusions of this work. The six highlighted green boxes are the newly replaced images. ![file] Figure 7. (d) Immunohistochemical expression of Topo IIu03b1 and RPA in different tumor tissues. The image used was representative of three independent experiments. The scale bar is 20 u03bcm. ,