Year-end Sale % OFF 
Abstract
Metastatic castration-resistant prostate cancer is commonly treated with chemotherapy, whose effect is less than satisfactory. This raised the need for novel agents for the treatment of prostate cancer. In the present study, five phthalimide-based curcumin derivatives were synthesized and completely characterized to assess improved stability, pharmacodynamics, and radical scavenging ability. To investigate the potential application in anti-cancer therapy, the anti-proliferative activity of the synthesized molecules was determined on aggressive prostate tumor cells. We demonstrated that the K3F21 derivative has increased potency compared to curcumin, in terms of GI50, anti-proliferative and anti-migrating activities. K3F21 inhibits anchorage-dependent and -independent growth of prostate cancer cells by altering the expression of key genes controlling cell proliferation, such as Cylins D1, B1 and B2, and apoptosis, among which Puma, Noxa, and Bcl-2 family members. Finally, the anti-cancer activity of K3F21 was demonstrated by the analysis of cancer-associated PI3K/AKT, ERK, and p38 signaling pathways.
Highlights
Prostate cancer (PCa) is the second most commonly diagnosed cancer and leading cause of cancer death in western males [1]
We demonstrated that the K3F21 derivative has increased potency compared to curcumin, in terms of growth is inhibited by 50% (GI50), anti-proliferative and anti-migrating activities
When the reaction is accomplished in N,N-dimethylformamide (DMF), the product separates by acidification with hydrochloric acid
Summary
Prostate cancer (PCa) is the second most commonly diagnosed cancer and leading cause of cancer death in western males [1]. Curcumin (1,7-bis [4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-Dione), a polyphenol obtained from the rhizome Curcuma longa L., and its analogs have shown anti-cancer properties by suppressing tumor initiation and progression [6,7], through the modulation of multiple signaling pathways and the inhibition of cell proliferation, invasion, metastasis, and angiogenesis [8]. Curcumin has been recently found to affect cancer associated fibroblast (CAF)-driven PCa invasion, promoted by prostate tumor–stromal interaction, through the inhibition of the MAOA/mTOR/HIF-1α signaling pathway [11]. These data pointed at curcumin as a protective molecule against the epithelial to mesenchymal transition (EMT), a highly complex process allowing the cells to escape from the primary tumor and disseminate at distant sites. We describe the synthesis, chemical and pharmacokinetic characterization, and anti-proliferative activity of new phthalimide-based curcumin derivatives on human PCa cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
