Liposomal Curcumin Targeting Endometrial Cancer Through the NF-κB Pathway

Abstract

Background/Aims: Emerging evidence suggests that curcumin possesses chemopreventive properties against various cancers. However, its poor bioavailability limits its clinical application. In this study, we aimed to utilize encapsulation in liposomes (Lipo) as a strategy for the clinical administration of curcumin for endometrial carcinoma (EC). Methods: Curcumin was encapsulated in a liposomal delivery system to prepare a formulation of liposomal curcumin (LC). EC cell lines Ishikawa and HEC-1 were treated with the compound and cell proliferation was measured using MTT assay. Hoechst 33258 staining assay and flow cytometry were used to detect apoptosis of the cells. Wound healing and cell invasion assays were employed to monitor cell motility. Underlying target signaling, such as NF-κB, caspases, and MMPs, were further studied via qRT-PCR and western blot. Thereafter, a zebrafish model was used to assess the toxicity of LC. Finally, a zebrafish transplantation tumor model of EC was grown and treated with LC. Tumors were monitored and harvested to study the expression of NF-κB. Results: The formation of LC was successfully developed with excellent purity and physical properties. In vitro, LC resulted in dose-dependent inhibition of proliferation, induction of apoptosis, and suppression of Ishikawa and HEC-1 cell motility. LC treatment also suppressed the activation and/or expression of NF-κB, caspase-3, and MMP-9. No demonstrable toxicity was found in the zebrafish model and tumors were suppressed after treatment with LC. PCR analysis also showed down-regulated expression of NF-κB. Conclusions: LC was successfully prepared and played biological roles against EC probably through negative regulation of the NF-κB pathway in vitro and in vivo, which demonstrates its potential therapeutic effects in EC.

Sotetsuflavone inhibits proliferation and induces apoptosis of A549 cells through ROS-mediated mitochondrial-dependent pathway

“…The cells in the six-well plate were treated as described in the part of cell apoptosis analysis experiment. The cells were washed three times with pre-cooled PBS and then fixed with 4% paraformaldehyde for 30 min, the appropriate amount of Hoechst was added dropwise to the plate after washing with PBS for three times and incubated at room temperature for 15 min, PBS washed three times, then, observed under a fluorescence microscope and photographed [ 21 ].…”

<p>Curcumin Inhibited Podocyte Cell Apoptosis and Accelerated Cell Autophagy in Diabetic Nephropathy via Regulating Beclin1/UVRAG/Bcl2</p>

“…[19][20][21] The studies have found that curcumin inhibits cell proliferation and induces apoptosis in several tumors. [22][23][24][25] Besides, curcumin has been reported to enhance autophagy-related cell death, 26 and induce cell apoptosis through lysosomal membrane permeabilization-medicated autophagy or downregulating lncRNA. 27,28 What's more, curcumin exerts protective effects through promoting autophagy and ameliorating apoptosis in diabetic cardiomyopathy.…”

<p>Curcumin and endometrial carcinoma: an old spice as a novel agent</p>

“…The in vivo pharmacokinetics of CUR-M was evaluated as promising (in Wistar rodent model) after intravenous administration 37. In a similar study on Ishikawa and HEC-1 cells, liposomal curcumin (LC), prepared by encapsulating curcumin in a liposomal delivery system, downregulated the expression of NF-κB proteins (nuclear factor kappa light chain enhancer of activated B cells),39 which control DNA transcription and cytokine production,40 hence leading to the decrease in the levels of various core molecules such as pro-apoptotic caspase-341 and extracellular matrix degrader MMP-9 42. These in vitro experiments revealed that the treatment of EC cells with LC leads to the inhibition of proliferation, induction of apoptosis, and suppression of cell motility 39…”