1. A novel quinazolinone chalcone derivative induces mitochondrial dependent apoptosis and inhibits PI3K/Akt/mTOR signaling pathway in human colon cancer HCT-116 cells.
- Author
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Wani ZA, Guru SK, Rao AV, Sharma S, Mahajan G, Behl A, Kumar A, Sharma PR, Kamal A, Bhushan S, and Mondhe DM
- Subjects
- Animals, Cell Cycle drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Chalcones chemistry, Humans, Membrane Potential, Mitochondrial drug effects, Mice, Molecular Structure, Neoplasms, Experimental drug therapy, Phosphatidylinositol 3-Kinases genetics, Proto-Oncogene Proteins c-akt genetics, Quinazolinones chemistry, Random Allocation, Signal Transduction drug effects, TOR Serine-Threonine Kinases genetics, Apoptosis drug effects, Chalcones pharmacology, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Quinazolinones pharmacology, TOR Serine-Threonine Kinases metabolism
- Abstract
We have synthesized a novel quinazolinone chalcone derivative (QC) and first time reported its in-vitro and in-vivo anticancer potential. It inhibited the cell proliferation of different cancer cell lines like PC-3, Panc-1, Mia-Paca-2, A549, MCF-7 and HCT-116. It induces apoptosis as measured by several biological endpoints such as apoptotic body formation, evident by Hoechst and scanning electron microscopy, enhanced annexinV-FITC binding of the cells, increased sub-G0 cell fraction, loss of mitochondrial membrane potential (Δψm), reduction of Bcl-2/Bax ratio, activation of caspase-9, caspase-3 and PARP-1 (poly-ADP Ribose polymerase) cleavage in HCT-116 cells. In spite of apoptosis, QC significantly hammers the downstream and upstream signaling cascade of PI3K/Akt/mTOR pathway and cell cycle regulator Skp-2, p21 and p27. Interestingly, QC induces the S and G2/M phase of HCT-116 cells at experimental doses. QC inhibits the tumor growth of Ehrlich ascites carcinoma (EAC), Ehrlich tumor (ET, solid) and sarcoma-180(solid) mice models. Furthermore, it was found to be non-toxic as no animal mortality (0/7) occurred during experimental doses. The present study provides an insight of anticancer potential of QC, which may be useful in managing and treating cancer., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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