Nanoliposomal formulation encapsulating celecoxib and genistein inhibiting COX-2 pathway and Glut-1 receptors to prevent prostate cancer cell proliferation
Author links open overlay panelJingyanTianaFengjunGuobYingyingChenaYanqingLiaBingbingYuaYangLia
a
Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021, Jilin, PR China
b
Department of Gynaecology and Obstetrics, The Second Hospital of Jinlin University, 218 Ziqiang Street, Changchun, 130041, Jilin, PR China
Received 13 November 2018, Revised 18 December 2018, Accepted 8 January 2019, Available online 20 January 2019.
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doi.org/10.1016/j.canlet.20... rights and content
Highlights
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The manuscript discusses about the method of synthesis of a nanoliposomal formulation containing celecoxib and genistein drugs together in one platform.
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Cell viability results show that these drugs inhibit the growth of prostate cancer cells when used in combination.
Supporting the role of genistein towards inhibition of Glut-1 receptors, we observed that glucose uptake was decreased after the treatment of prostate cancer cells with the liposomal formulation containing both the drugs.
Most importantly, the developed nanoliposomal formulation was nontoxic to the normal fibroblasts cells.
Genomic and proteomic data suggest that expression of genes and proteins involved in anti-apoptosis and growth of prostate cancer cells were decreased.
Abstract
Globally, prostate cancer remains a challenging health burden for men as it is the second leading cause of cancer death in men and about one in nine will be diagnosed with prostate cancer in his lifetime. Enhanced expression of COX-2 and Glut-1 proteins are reported as major factors leading to the origin and progress of prostate cancer through modulating the associated signaling pathways. In this study, we have synthesized a multifunctional liposomal system containing celecoxib and genistein drugs. The combinatorial effect of these drugs leads to the selectively induce the apoptosis of prostate cancer cells than normal fibroblast cells. The mechanistic study suggests that enhanced reactive oxygen species (ROS) formation and a decrease in cellular GSH concentration, along with inhibition of COX-2 synthesis and Glut-1 receptors are the key processes behind the inhibition of prostate cancer cells. Overall, these results provide strong evidence for the role of COX-2 and Glut-1 proteins for the progression of prostate cancer and highlighting the potential of celecoxib and genistein as a useful and combinatorial pharmacological agent for chemotherapeutic purposes in prostate cancer.