Curcumin Analogue CA15 Exhibits Anticancer Effects on HEp-2 Cells via Targeting NF-κB

Abstract

Laryngeal carcinoma remains one of the most common malignancies, and curcumin has been proven to be effective against head and neck cancers in vitro. However, it has not yet been applied in clinical settings due to its low stability. In the current study, we synthesized 34 monocarbonyl analogues of curcumin with stable structures. CA15, which exhibited a stronger inhibited effect on laryngeal cancer cells HEp-2 but a lower toxicity on hepatic cells HL-7702 in MTT assay, was selected for further analysis. The effects of CA15 on cell viability, proliferation, migration, apoptosis, and NF-κB activation were measured using MTT, Transwell migration, flow cytometry, Western blot, and immunofluorescence assays in HEp-2 cells. An NF-κB inhibitor, BMS-345541, as well as curcumin was also tested. Results showed that CA15 induced decreased toxicity towards HL-7702 cells compared to curcumin and BMS-345541. However, similar to BMS-345541 and curcumin, CA15 not only significantly inhibited proliferation and migration and induced caspase-3-dependent apoptosis but also attenuated TNF-α-induced NF-κB activation in HEp-2 cells. These results demonstrated that curcumin analogue CA15 exhibited anticancer effects on laryngeal cancer cells via targeting of NF-κB.

Effect of combination of curcumin and GLUT‐1 AS‐ODN on radiosensitivity of laryngeal carcinoma through regulating autophagy

“…38 Curcumin also has the anti-tumor function on laryngeal cancer cells via regulating NF-κB and JAK-2/ STAT-3 signaling pathway. 39,40 These data reveal that curcumin might be served as a tumor suppressor in the development of laryngeal carcinoma. At present, numerous evidences suggest that curcumin can also sensitize diverse types of malignant tumor to irradiation.…”

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…1 The anti-cancer compounds from Chinese herbal medicine (CHM). The popular anti-cancer compounds in CHM presented as a "word cloud", in which the size of each name is proportional to the number of publications of the compounds (NF-κB), signal transducer and activator of transcription and cell cycle-related proteins [36][37][38][39][40][41][42][43][44][45][46]. Curcumin is shown to induce anti-cancer activities through the disruption of mitochondrial membrane potential and blockade at G2/M phase of the cell cycle in human epidermoid carcinoma A-431 cells [47].…”

Curcuminoids: Implication for inflammation and oxidative stress in cardiovascular diseases

“…Thus, a series of synthetic modification, phosphatidylcholine formulations, lipid complexes, solid dispersions, prodrugs, microspheres, analogues, derivatives, and nanoscale formulations, to curcumin have been intensively studied in order to develop a molecule with enhanced bioactivities (Markatou et al, ; Paradkar, Ambike, Jadhav, & Mahadik, ; Sivasami & Hemalatha, ). Currently, there are many different proposed strategies regarding synthetically improving its stability and activity; from side chain and diketone transformations to alkyl and alkenyl functionalization on C‐4, many have been reported (Gyuris et al, ) to ultimately create curcumin analogues such as C66 (Y. Wang et al, ), CA15 (J. Chen, Zhang, et al, ), A13 (Revalde et al, ), and NCB‐02 (Usharani, Mateen, Naidu, Raju, & Chandra, ). Conjugates of curcumin with β‐cyclodextrin and γ‐cyclodextrin, liposomal and loaded nanoparticles, and nanoemulsion are some of the lipid‐based colloidal systems that have been employed to enhance its release, water solubility, and bioavailability (Jordan et al, ).…”