Evodiamine inactivates NF-κB and potentiates the antitumor effects of gemcitabine on tongue cancer both in vitro and in vivo

Abstract

ObjectiveThe aim of this study was to investigate whether evodiamine (EVO) could potentiate the antitumor activity of gemcitabine (GEM) in tongue cancer cells and determine its potential underlying mechanisms.Materials and methodsHuman Tca8113 and CAL-27 tongue squamous carcinoma cell lines were treated with EVO and GEM in different sequences and doses, after which cell proliferation was measured. Drug interactions were analyzed using the Chou–Talalay method with CompuSyn software. Clonality, apoptosis, and migration were measured using the plate clone formation assay, annexin V/propidium iodide (PI) staining, Hoechst 33342 staining, and the wound-healing test. The activity of the nuclear factor kappa light-chain enhancer of activated B cell (NF-κB) p65 subunit and its downstream proteins was quantified by Western blotting. The effects of the drug combination in vivo were assessed using a CAL-27 heterotopic xenograft model.ResultsEVO and GEM had synergistic effects on CAL-27 and Tca8113 cell lines in time- and concentration-dependent manners. Combination of drugs inhibited cell proliferation and migration and reduced the expression of NF-κB p65, B cell lymphoma 2 (Bcl-2), and B cell lymphoma extra large (Bcl-xl) compared with the control and either drug alone. In vivo, combination treatment of the xenograft model with EVO and GEM led to a significant reduction in tumor volume growth and inhibited the activation of NF-κB p65 with no obvious adverse reactions.ConclusionThe results of this study showed that EVO may inhibit cancer cells by suppressing NF-κB activity, and in combination with GEM, it may increase the chemosensitivity of tongue squamous cancer cells, thereby improving the treatment response.

BMP9 mediates the anticancer activity of evodiamine through HIF‑1α/p53 in human colon cancer cells

“…In the present study, the effective anticancer activity of Evo, which may be mediated by BMP9 via the upregulation of HIF-1α to partly increase the activity of p53, was demonstrated in human colon cancer. It has been reported that Evo exhibits great anti-cancer activities in many types of cancer, such as tongue, breast, colon, prostate and lung cancer (9)(10)(11)(12)26,27). As far as colon cancer is concerned, the anticancer activity of Evo may be mediated by inactivating the NF-κB (9) or TGF-β1 (11), or activating the p53/p21/Rb pathway (12).…”

“…Evodiamine (Evo), a quinolone alkaloid extracted from traditional herbal medicine Evodia rutaecarpa (7), has multiple pharmacological actions and could be used for obesity, inflammation, infectious and cardiovascular diseases (8). A growing amount of evidence has indicated that Evo exhibits anticancer activity against various types of cancer, such as tongue, colon and breast cancer (9)(10)(11)(12). According to studies, this activity of Evo may be mediated by NF-κB (9), transforming growth factor β1 (TGF-β1) (11) and/or the p53/p21/Rb pathway (12).…”

“…A growing amount of evidence has indicated that Evo exhibits anticancer activity against various types of cancer, such as tongue, colon and breast cancer (9)(10)(11)(12). According to studies, this activity of Evo may be mediated by NF-κB (9), transforming growth factor β1 (TGF-β1) (11) and/or the p53/p21/Rb pathway (12). However, the explicit mechanism underlying this activity requires further exploration.…”

Peroxidase-mimicking evodiamine/indocyanine green nanoliposomes for multimodal imaging-guided theranostics for oral squamous cell carcinoma

“…Studies also showed that EVO would be a potential therapeutic drug against other diseases such as hypomotility disorders [ 25 ], renal tubulointerstitial fibrosis [ 26 ], and IgE-induced allergenic diseases (including rhinitis and atopic dermatitis) [ 27 ]. Recently, EVO was widely reported to have the potential to become a therapeutic medicine for treating various cancers [ 28 , 29 ] due to its ability to cause tumor cell apoptosis by suppressing the NF-κB activity on tongue cancers both in vitro and in vivo [ 30 ]. A famous pill called Zuojin Pills, containing EVO, could be used for hepatocellular carcinoma treatment [ 31 ].…”

Nitric Oxide Inhibits NF-κB-mediated Survival Signaling: Possible Role in Overcoming TRAIL Resistance

“…Several studies have shown that TRAIL induces apoptosis in cancer cells but simultaneously activates NF-ĸB (32)(33)(34)(35)(36). Additionally, we showed that several chemotherapeutic agents activate NF-ĸB survival signaling (37) and agents, including nitric oxide-donors, that inhibit NF-ĸB can potentiate anti-tumor activity (37)(38)(39). NO has been to shown to sensitize TRAILresistant tumors to TRAIL via inhibition of NF-kB (40,41).…”