A New Chalcone Derivative with Promising Antiproliferative and Anti-Invasion Activities in Glioblastoma Cells

Abstract

Glioblastoma (GBM) is the most common and most deadly primary malignant brain tumor. Current therapies are not effective, the average survival of GBM patients after diagnosis being limited to few months. Therefore, the discovery of new treatments for this highly aggressive brain cancer is urgently needed. Chalcones are synthetic and naturally occurring compounds that have been widely investigated as anticancer agents. In this work, three chalcone derivatives were tested regarding their inhibitory activity and selectivity towards GBM cell lines (human and mouse) and a non-cancerous mouse brain cell line. The chalcone 1 showed the most potent and selective cytotoxic effects in the GBM cell lines, being further investigated regarding its ability to reduce critical hallmark features of GBM and to induce apoptosis and cell cycle arrest. This derivative showed to successfully reduce the invasion and proliferation capacity of tumor cells, both key targets for cancer treatment. Moreover, to overcome potential systemic side effects and its poor water solubility, this compound was encapsulated into liposomes. Therapeutic concentrations were incorporated retaining the potent in vitro growth inhibitory effect of the selected compound. In conclusion, our results demonstrated that this new formulation can be a promising starting point for the discovery of new and more effective drug treatments for GBM.

Chalcone 9X Contributed to Repressing Glioma Cell Growth and Migration and Inducing Cell Apoptosis by Reducing FOXM1 Expression In Vitro and Repressing Tumor Growth In Vivo

“…In this study, we found that Chalcone 9X showed a lower cytotoxic effect than Chalcones 1 for human normal cell lines, and the security is much better than Chalcones 1. 100 μ mol/L Chalcone 9X had little cytotoxicity to normal astrocyte HA1800 cells, while 100 μ mol/L Chalcone 1 showed very high cytotoxicity to nontumor cell line [ 15 ].…”

“…Chalcones have been demonstrated to inhibit tumor progression and development in cancers [12][13][14][15][16][17][18], including glioma [15,18]. The synthetic Chalcone 9X is an aromatic ketone, which has been proved to own antitumor activities in lung cancer cells and hepatic cancer cells through activating Caspase-3 and Caspase-8 signaling pathway [19].…”

“…Natural and chemical synthetic chalcones have been revealed to play critical roles in some biological functions, such as inflammation [7][8][9] and antibacterial effects [10,11]. Furthermore, more studies demonstrated that chalcones could inhibit tumor progression in various cancers [12][13][14][15][16][17][18][19], including glioma [15,18]. For example, Mendanha et al found that Chalcone 1 could induce cell apoptosis of glioblastoma (GBM), which was triggered by the cell cycle arrest in the G2/M checkpoint, and might be a potential to provide a new treatment alternative for GBM 15 .…”

“…Furthermore, more studies demonstrated that chalcones could inhibit tumor progression in various cancers [12][13][14][15][16][17][18][19], including glioma [15,18]. For example, Mendanha et al found that Chalcone 1 could induce cell apoptosis of glioblastoma (GBM), which was triggered by the cell cycle arrest in the G2/M checkpoint, and might be a potential to provide a new treatment alternative for GBM 15 . Moreover, Wang et al also discovered that flavokawain B (FKB), a natural kava chalcone, induced protective autophagy signaling pathway in GBM cells, which indicated that the combination treatment of FKB with autophagy inhibitors might be an effective strategy for GBM 18 .…”

Recent Advances in Bioactive Flavonoid Hybrids Linked by 1,2,3-Triazole Ring Obtained by Click Chemistry

“…The scaffold associated to flavonoids is very versatile and has long been recognized for the wide range of pharmacological activities, such as anti-inflammatory, cardioprotective, antimicrobial, anticancer, and neuroprotective [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ]. The interest in these compounds in Medicinal Chemistry is evidenced by the fact that several flavonoids have been marketed or clinically tested for various health conditions.…”