Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells

This study shows that the non-steroidal anti-inflammatory drug (NSAID) celecoxib and its non-cyclooxygenase-2 (COX2) analogue dimethylcelecoxib (DMC) exert a potent inhibitory effect on the growth of human cervix HeLa multi-cellular tumor spheroids (MCTS) when added either at the beginning (“preventive protocol”; IC50 = 1 ± 0.3 nM for celecoxib and 10 ± 2 nM for DMC) or after spheroid formation (“curative protocol”; IC50 = 7.5 ± 2 µM for celecoxib and 32 ± 10 µM for DMC). These NSAID IC50 values were significantly lower than those attained in bidimensional HeLa cells (IC50 = 55 ± 9 µM celecoxib and 48 ± 2 µM DMC) and bidimensional non-cancer cell cultures (3T3 fibroblasts and MCF-10A mammary gland cells with IC50 from 69 to >100 µM, after 24 h). The copper-based drug casiopeina II-gly showed similar potency against HeLa MCTS. Synergism analysis showed that celecoxib, DMC, and casiopeinaII-gly at sub-IC50 doses increased the potency of cisplatin, paclitaxel, and doxorubicin to hinder HeLa cell proliferation through a significant abolishment of oxidative phosphorylation in bidimensional cultures, with no apparent effect on non-cancer cells (therapeutic index >3.6). Similar results were attained with bidimensional human cervix cancer SiHa and human glioblastoma U373 cell cultures. In HeLa MCTS, celecoxib, DMC and casiopeina II-gly increased cisplatin toxicity by 41–85%. These observations indicated that celecoxib and DMC used as adjuvant therapy in combination with canonical anti-cancer drugs may provide more effective alternatives for cancer treatment.

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Primula vulgaris extract induces cell cycle arrest and apoptosis in human cervix cancer cells

Journal of Pharmaceutical Analysis ◽

10.1016/j.jpha.2018.05.003 ◽

2018 ◽

Vol 8 (5) ◽

pp. 307-311 ◽

Cited By ~ 10

Author(s):

Selim Demir ◽

Ibrahim Turan ◽

Rezzan Aliyazicioglu ◽

Serap Ozer Yaman ◽

Yuksel Aliyazicioglu

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Cervix Cancer ◽

Cycle Arrest ◽

Primula Vulgaris ◽

Human Cervix

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Benzophenone and Benzoylphloroglucinol Derivatives from Hypericum sampsonii with Anti-Inflammatory Mechanism of Otogirinin A

Molecules ◽

10.3390/molecules25194463 ◽

2020 ◽

Vol 25 (19) ◽

pp. 4463 ◽

Cited By ~ 1

Author(s):

Chun-Yi Huang ◽

Tzu-Cheng Chang ◽

Yu-Jing Wu ◽

Yun Chen ◽

Jih-Jung Chen

Keyword(s):

Nitric Oxide ◽

Inhibitory Effect ◽

No Production ◽

Necrosis Factor Alpha ◽

Aerial Parts ◽

Arginase 1 ◽

Potent Inhibition ◽

Ic50 Values ◽

Cytokine Tumor Necrosis Factor ◽

Anti Inflammatory

Three new compounds, 4-geranyloxy-2-hydroxy-6-isoprenyloxybenzophenone (1), hypericumone A (2) and hypericumone B (3), were obtained from the aerial parts of Hypericum sampsonii, along with six known compounds (4–9). The structures of these compounds were determined through spectroscopic and MS analyses. Hypericumone A (2), sampsonione J (8) and otogirinin A (9) exhibited potent inhibition (IC50 values ≤ 40.32 μM) against lipopolysaccharide (LPS)-induced nitric oxide (NO) generation. Otogirinin A (9) possessed the highest inhibitory effect on NO production with IC50 value of 32.87 ± 1.60 μM. The well-known proinflammatory cytokine, tumor necrosis factor-alpha (TNF-α) was also inhibited by otogirinin A (9). Western blot results demonstrated that otogirinin A (9) downregulated the high expression of inducible nitric oxide synthase (iNOS). Further investigations on the mechanism showed that otogirinin A (9) blocked the phosphorylation of MAPK/JNK and IκBα, whereas it showed no effect on the phosphorylation of MAPKs/ERK and p38. In addition, otogirinin A (9) stimulated anti-inflammatory M2 phenotype by elevating the expression of arginase 1 and Krüppel-like factor 4 (KLF4). The above results suggested that otogirinin A (9) could be considered as potential compound for further development of NO production-targeted anti-inflammatory agent.

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Anti-Inflammatory Flavonolignans from Triticum aestivum Linn. Hull

Applied Sciences ◽

10.3390/app10238656 ◽

2020 ◽

Vol 10 (23) ◽

pp. 8656

Author(s):

Ah-Reum Han ◽

Yun-Seo Kil ◽

Min Jeong Hong ◽

Jisu Park ◽

Hyeon Hwa Park ◽

...

Keyword(s):

Triticum Aestivum ◽

Crop Production ◽

Ethyl Acetate Fraction ◽

Inhibitory Effect ◽

Raw 264.7 Cells ◽

No Production ◽

Phytochemical Investigation ◽

Ic50 Values ◽

Anti Inflammatory ◽

Food Grain

Wheat (Triticum aestivum Linn.; Poaceae) is a very common and important food grain and ranks second in total cereal crop production. A large amount of wheat hull is produced after threshing that, as the non-food part of wheat, is agro-waste, accounting for 15~20% of the wheat. This study aimed at biologically and phytochemically investigating wheat hull for its valorization as a by-product. In our ongoing search for natural product-derived anti-inflammatory agents, T. aestivum hull was evaluated for its nitric oxide (NO) production inhibition in lipopolysaccharide (LPS)-activated RAW 264.7 cells, and the phytochemical investigation of the ethyl acetate fraction showing inhibitory effect led to the isolation of a flavone (1) and seven flavonolignans (2–8). Compounds 2–8 have not yet been isolated from Triticum species. All compounds were evaluated for their LPS-induced NO production inhibition, and 1, 2, 4, 6, and 8 exhibited inhibitory effects with IC50 values ranging from 24.14 to 58.95 μM. These results suggest the potential of using T. aestivum hull as a source for producing anti-inflammatory components, enhancing its valorization as a by-product.

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The NF-κB Signaling and Wnt/β-catenin Signaling in MCF-7 Breast Cancer Cells in Response to Bioactive Components from Mushroom Antrodia Camphorata

The American Journal of Chinese Medicine ◽

10.1142/s0192415x21500117 ◽

2020 ◽

pp. 1-17

Author(s):

Ting-Chun Lin ◽

Alison Germagian ◽

Zhenhua Liu

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Inhibitory Effect ◽

Luciferase Assay ◽

Bioactive Components ◽

Antrodia Camphorata ◽

Anticancer Properties ◽

Anti Inflammatory ◽

Mcf 7

Breast cancer is the leading cancer, accounting for approximately 15% cancer deaths in women worldwide. This study investigated the anti-inflammation and anticancer properties of two bioactive components from Antrodia camphorata(AC), a rare medicinal mushroom natively grown in Taiwan and commonly used in Chinese traditional medicine. The anti-inflammatory and antitumorigenic functions of Antroquinonol (AQ) and 4-Acetylantroquinonol B (4-AAQB) from AC were examined on breast cancer cell line MCF-7 with/without TNF-[Formula: see text] stimulation. Among nine inflammatory mediators (IL6, IL10, IL1[Formula: see text], IFN[Formula: see text], PTGS2, TGF[Formula: see text]1, TNF-[Formula: see text], CCL2 andCSF1) examined, AQ inhibited two of them (IL-10 and PTGS2), while 4-AAQB inhibited three of them (IL-10, PTGS2 andTNF-[Formula: see text] ([Formula: see text]¡ 0.05). TNF-[Formula: see text] stimulated expressions of five mediators (IL6, IL10, IFN[Formula: see text], PTGS2, and CCL2), and AQ and 4-AAQB inhibited IL6 elevation ([Formula: see text]¡ 0.05). Both components inhibited aromatase expression with/without TNF-[Formula: see text] stimulation, with 4-AAQB to be more effective ([Formula: see text]¡ 0.05). For immune checkpoint CD47, both components inhibited CD47 expression ([Formula: see text]¡ 0.05), but it did not respond to TNF-[Formula: see text] stimulation. For Wnt/[Formula: see text]- catenin signaling downstream genes (CCND1, C-MYC and AXIN2), both components have significant or marginal inhibitory effect on C-MYC in the condition with/without TNF-[Formula: see text] stimulation. The luciferase assay demonstrated that both components exhibited inhibitory effect on NF-[Formula: see text]B signaling and Wnt/[Formula: see text]-catenin signaling in the condition without TNF-[Formula: see text] stimulation. In conclusion, our results displayed an overall pattern that AQ and 4-AAQB possess potential anti-inflammatory and antitumorigenic functions in MCF-7 breast cancer cells and warranted further in vivo pre-clinical and clinical studies to explore their anticancer properties.

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PKCε is essential for gelsolin expression by histone deacetylase inhibitor apicidin in human cervix cancer cells

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2007.01.046 ◽

2007 ◽

Vol 354 (3) ◽

pp. 769-775 ◽

Cited By ~ 11

Author(s):

Dae-Wook Eun ◽

Seong Hoon Ahn ◽

Jeong Soo You ◽

Jong Woo Park ◽

Eun Kyung Lee ◽

...

Keyword(s):

Cancer Cells ◽

Histone Deacetylase ◽

Histone Deacetylase Inhibitor ◽

Cervix Cancer ◽

Deacetylase Inhibitor ◽

Human Cervix

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Water Soluble C 60 -Liposome and the Biological Effect of C 60 to Human Cervix Cancer Cells

Chinese Physics Letters ◽

10.1088/0256-307x/11/4/005 ◽

1994 ◽

Vol 11 (4) ◽

pp. 207-210 ◽

Cited By ~ 11

Author(s):

Wenzhu Li (Wenzhou Li) ◽

Kaixian Qian ◽

Wendong Huang ◽

Xinxin Zhang ◽

Wanxi Chen

Keyword(s):

Cancer Cells ◽

Biological Effect ◽

Water Soluble ◽

Cervix Cancer ◽

Soluble C ◽

Water Soluble C ◽

Human Cervix

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Structural Design, Synthesis and Antioxidant, Antileishmania, Anti-Inflammatory and Anticancer Activities of a Novel Quercetin Acetylated Derivative

Molecules ◽

10.3390/molecules26226923 ◽

2021 ◽

Vol 26 (22) ◽

pp. 6923

Author(s):

Saul Vislei Simões da Silva ◽

Orlando Maia Barboza ◽

Jéssica Teles Souza ◽

Érica Novaes Soares ◽

Cleonice Creusa dos Santos ◽

...

Keyword(s):

Cancer Cells ◽

Cell Cultures ◽

Biological Effects ◽

Lung Fibroblasts ◽

C6 Glioma Cells ◽

Anticancer Activities ◽

Healthy Human ◽

Rat Glioma ◽

Biological Potential ◽

Anti Inflammatory

Quercetin (Q) is a bioflavonoid with biological potential; however, poor solubility in water, extensive enzymatic metabolism and a reduced bioavailability limit its biopharmacological use. The aim of this study was to perform structural modification in Q by acetylation, thus, obtaining the quercetin pentaacetate (Q5) analogue, in order to investigate the biological potentials (antioxidant, antileishmania, anti-inflammatory and cytotoxicity activities) in cell cultures. Q5 was characterized by FTIR, 1H and 13C NMR spectra. The antioxidant potential was evaluated against the radical ABTS•+. The anti-inflammatory potential was evaluated by measuring the pro-inflammatory cytokine tumor necrosis factor (TNF) and the production of nitric oxide (NO) in peritoneal macrophages from BALB/c mice. Cytotoxicity tests were performed using the AlamarBlue method in cancer cells HepG2 (human hepatocarcinoma), HL-60 (promyelocytic leukemia) and MCR-5 (healthy human lung fibroblasts) as well as the MTT method for C6 cell cultures (rat glioma). Q and Q5 showed antioxidant activity of 29% and 18%, respectively, which is justified by the replacement of hydroxyls by acetyl groups. Q and Q5 showed concentration-dependent reductions in NO and TNF production (p < 0.05); Q and Q5 showed higher activity at concentrations > 40µM when compared to dexamethasone (20 µM). For the HL-60 lineage, Q5 demonstrated selectivity, inducing death in cancer cells, when compared to the healthy cell line MRC-5 (IC50 > 80 µM). Finally, the cytotoxic superiority of Q5 was verified (IC50 = 11 µM), which, at 50 µM for 24 h, induced changes in the morphology of C6 glioma cells characterized by a round body shape (not yet reported in the literature). The analogue Q5 had potential biological effects and may be promising for further investigations against other cell cultures, particularly neural ones.

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