chrysin and Adenocarcinoma

Pancreatic adenocarcinoma (PDAC) and lung cancer are expected to represent the most common cancer types worldwide until 2030. Under typical conditions, mitochondria provide the bulk of the energy needed to sustain cell life. For that inhibition of mitochondrial complex ΙΙ (CΙΙ) and ubiquinone oxidoreductase with natural treatments may represent a promising cancer treatment option. A naturally occurring flavonoid with biological anti-cancer effects is chyrsin. Due to their improved bioavailability, penetrative power, and efficacy, chitosan-chrysin nano-formulations (CCNPs) are being used in medicine with increasing frequency. Chitosan (cs) is also regarded as a highly versatile and adaptable polymer. The cationic properties of Cs, together with its biodegradability, high adsorption capacity, biocompatibility, effect on permeability, ability to form films, and adhesive properties, are advantages. In addition, Cs is thought to be both safe and economical. CCNPs may indeed be therapeutic candidates in the treatment of pancreatic adenocarcinoma (PDAC) and lung cancer by blocking succinate ubiquinone oxidoreductase.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Chitosan; Flavonoids; Humans; Lung Neoplasms; Nanoparticles; Pancreatic Neoplasms; Succinate Dehydrogenase; Ubiquinone

Either apigenin or chrysin alone has been found to exert anti-inflammatory and tumor suppressive effect. However, the combined effect of apigenin and chrysin on colorectal cancer (CRC) has not been fully clarified. We attempted to explore the effect of chrysin and apigenin on CRC and its related mechanism. SW480 and HCT-116 cells were treated with either apigenin or chrysin alone or two-drug combination at different doses of 5, 25, 50, 100 μM for optimal concentration determination. Then, we focused on the individual and combined effect of apigenin and chrysin on clonogenicity, apoptosis, metastasis-related behaviors of CRC cells by colony formation assay, cell scratch assay, flow cytometry, and transwell assay. The changes of the activation of P38-MAPK/AKT pathway were evaluated underlying apigenin and chrysin intervention, further after co-treated with P38-MAPK agonist anisomycin. Apigenin (25 μM) combined with chrysin (25 μM) were determined to be optimal. Treatment with the combination of apigenin (25 μM) and chrysin (25 μM) significantly reduced cell clone numbers, migration, and invasion ability, while increased the cell apoptosis in both CRC cell lines. The combined effect was higher than chrysin or apigenin alone. Meanwhile, p-P38 and p-AKT were significantly downregulated by chrysin and apigenin treatment. The tumor inhibitive effect of apigenin combined with chrysin was obviously reversed by adding P38 agonist, anisomycin. Apigenin (25 μM) combined with chrysin (25 μM) showed synergetic effect in inhibiting the growth and metastasis of CRC cells by suppressing the activity of P38-MAPK/AKT pathway.

Topics: Adenocarcinoma; Anisomycin; Apigenin; Apoptosis; Cell Line, Tumor; Cell Movement; Clone Cells; Colorectal Neoplasms; Drug Synergism; Flavonoids; HCT116 Cells; Humans; MAP Kinase Signaling System; Molecular Targeted Therapy; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; p38 Mitogen-Activated Protein Kinases; Proto-Oncogene Proteins c-akt; Tumor Stem Cell Assay

Vanadium compounds were studied during recent years to be considered as a representative of a new class of nonplatinum metal antitumor agents in combination to its low toxicity. On the other hand, flavonoids are a wide family of polyphenolic compounds synthesized by plants that display many interesting biological effects. Since coordination of ligands to metals can improve the pharmacological properties, we report herein, for the first time, a exhaustive study of the mechanisms of action of two oxidovanadium(IV) complexes with the flavonoids: silibinin Na₂[VO(silibinin)₂2]·6H₂O (VOsil) and chrysin [VO(chrysin)₂EtOH]₂(VOchrys) on human colon adenocarcinoma derived cell line HT-29. The complexes inhibited the cell viability of colon adenocarcinoma cells in a dose dependent manner with a greater potency than that the free ligands and free metal, demonstrating the benefit of complexation. The decrease of the ratio of the amount of reduced glutathione to the amount of oxidized glutathione were involved in the deleterious effects of both complexes. Besides, VOchrys caused cell cycle arrest in G2/M phase while VOsil activated caspase 3 and triggering the cells directly to apoptosis. Moreover, VOsil diminished the NF-kB activation via increasing the sensitivity of cells to apoptosis. On the other hand, VOsil inhibited the topoisomerase IB activity concluding that this is important target involved in the anticancer vanadium effects. As a whole, the results presented herein demonstrate that VOsil has a stronger deleterious action than VOchrys on HT-29 cells, whereby suggesting that Vosil is the potentially best candidate for future use in alternative anti-tumor treatments.

Topics: Adenocarcinoma; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Cisplatin; Colonic Neoplasms; Coordination Complexes; Flavonoids; Humans; Molecular Structure; Silybin; Silymarin; Vanadium

Honey is reported to contain various compounds such as antioxidants. Chrysin is a natural and biologically active compound extracted from honey. It possesses antioxidant properties and promotes cell death by perturbing cell cycle progression. We focused on the possible role that chrysin may act as a potential anticancer agent, and tested its biological activity and possible mechanisms in the human lung adenocarcinoma epithelial cell line.. Antiproliferative effect of honey and chrysin were determined by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay; DNA fragmentation was determined by gel electrophoresis assay; apoptosis was detected by flow cytometer; apoptosis-related gene expression was detected by reverse transcription polymerase chain reaction assay; and activation of caspase-3 and caspase-9 were evaluated by a colorimetric assay; Bax and Bcl-2 protein expression were also analysed by western blotting.. The results revealed that the cell viability decreased in a concentration- and time- dependent manner in the malignant cells treated with honey and chrysin in comparison with the nonmalignant cells. The IC50 values of honey against A549 cells were determined 15 ± 0.05% and 8 ± 0.05 % after 48 and 72h, respectively. The IC50 dose of chrysin was determined to be 49.2 ± 0.6 and 38.7 ± 0.8 μM at 48 and 72 h, respectively. Reactivity with Annexin V fluorescence antibody and propidium iodide showed that chrysin induced apoptosis in the lung cancer cells (p<0.001). Moreover, chrysin treatment resulted in the activation of caspase-3 and - 9 and an increase in the Bax/Bcl-2 ratio (p<0.01). Bax protein expression was increased but Bcl-2 protein expression decreased in chrysin-treated cells .Chrysin inhibits the growth of the lung cancer cells by inducing cancer cell apoptosis via the regulation of the Bcl-2 family and also activation of caspase-3 and -9, which may, in part, explain its anticancer activity.. This study shows that chrysin could also be considered as a promising chemotherapeutic agent and anticancer activity in treatment of the lung cancer cells in future.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Antineoplastic Agents; Apoptosis; bcl-2-Associated X Protein; Caspases; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Epithelial Cells; Flavonoids; Humans; Lung Neoplasms; Proto-Oncogene Proteins c-bcl-2; Structure-Activity Relationship; Tumor Cells, Cultured

Adjuvant therapies that enhance the anti-tumor effects of cis-diammineplatinum(II) dichloride (cisplatin, CDDP) are actively being pursued. Growing evidence supports the involvement of mitochondrial dysfunction in the anti-cancer effect of cisplatin. We examined the potential of using selective flavonoids that are effective in depleting tumor cells of glutathione (GSH) to potentiate cisplatin-mediated cytotoxicity in human lung adenocarcinoma (A549) cells. We found that cisplatin (40 microM, 48-h treatment) disrupts the steady-state levels of mitochondrial respiratory complex I, which correlates with elevated mitochondrial reactive oxygen species (ROS) production and cytochrome c release. The flavonoids, 2',5'-dihydroxychalcone (2',5'-DHC, 20 microM) and chrysin (20 microM) potentiated the cytotoxicity of cisplatin (20 microM), which could be blocked by supplementation of the media with exogenous GSH (500 microM). Both 2',5'-DHC and chrysin were more effective than the specific inhibitor of GSH synthesis, L-buthionine sulfoximine (BSO, 20 microM), in inducing GSH depletion and potentiating the cytotoxic effect of cisplatin. These data suggest that the flavonoid-induced potentiation of cisplatin's toxicity is due, in part, to synergetic pro-oxidant effects of cisplatin by inducing mitochondrial dysfunction, and the flavonoids by depleting cellular GSH, an important antioxidant defense.

Topics: Adenocarcinoma; Antineoplastic Agents; Cell Line, Tumor; Chalcones; Cisplatin; Drug Synergism; Electron Transport Complex I; Flavonoids; Glutathione; Humans; Lung Neoplasms; Mitochondria; Reactive Oxygen Species