Effect of 1-Carbaldehyde-3,4-dimethoxyxanthone on Prostate and HPV-18 Positive Cervical Cancer Cell Lines and on Human THP-1 Macrophages

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2021 Jul 2

PMID 34207168

Citations 1

Authors

Rui Medeiros

Bruno Horta

Joana Freitas-Silva

Jani Silva

Francisca Dias

Emilia Sousa

Madalena Pinto

Fatima Cerqueira

Affiliations

Soon will be listed here.

Abstract

Xanthone derivatives have shown promising antitumor properties, and 1-carbaldehyde-3,4-dimethoxyxanthone () has recently emerged as a potent tumor cell growth inhibitor. In this study, its effect was evaluated (MTT viability assay) against a new panel of cancer cells, namely cervical cancer (HeLa), androgen-sensitive (LNCaP) and androgen-independent (PC-3) prostate cancer, and nonsolid tumor derived cancer (Jurkat) cell lines. The effect of xanthone on macrophage functions was also evaluated. The effect of xanthone -conditioned THP-1 human macrophage supernatants on the metabolic viability of cervical and prostate cancer cell lines was determined along with its interference with cytokine expression characteristic of M1 profile (IL-1 ≤ β; TNF-α) or M2 profile (IL-10; TGF-β) (PCR and ELISA). Nitric oxide (NO) production by murine RAW264.7 macrophages was quantified by Griess reaction. Xanthone (20 μM) strongly inhibited the metabolic activity of the cell lines and was significantly more active against prostate cell lines compared to HeLa ( < 0.05). Jurkat was the cell most sensitive to the effect of xanthone . Compound -conditioned IL-4-stimulated THP-1 macrophage supernatants significantly ( < 0.05) inhibited the metabolic activity of HeLa, LNCaP, and PC-3. Xanthone did not significantly affect the expression of cytokines by THP-1 macrophages. The inhibiting effect of compound observed on the production of NO by RAW 264.7 macrophages was moderate. In conclusion, 1-carbaldehyde-3,4-dimethoxyxanthone () decreases the metabolic activity of cancer cells and seems to be able to modulate macrophage functions.

Citing Articles

Antitumor Effect of Chalcone Derivatives against Human Prostate (LNCaP and PC-3), Cervix HPV-Positive (HeLa) and Lymphocyte (Jurkat) Cell Lines and Their Effect on Macrophage Functions.

Horta B, Freitas-Silva J, Silva J, Dias F, Teixeira A, Medeiros R Molecules. 2023; 28(5).

PMID: 36903405 PMC: 10004497. DOI: 10.3390/molecules28052159.

References

He X, Shu J, Xu L, Lu C, Lu A . Inhibitory effect of Astragalus polysaccharides on lipopolysaccharide-induced TNF-a and IL-1β production in THP-1 cells. Molecules. 2012; 17(3):3155-64. PMC: 6268450. DOI: 10.3390/molecules17033155. View

Medeiros R, Morais A, Vasconcelos A, Costa S, Carrilho S, Oliveira J . Endothelial nitric oxide synthase gene polymorphisms and the shedding of circulating tumour cells in the blood of prostate cancer patients. Cancer Lett. 2002; 189(1):85-90. DOI: 10.1016/s0304-3835(02)00118-0. View

Wang M, Zhao J, Zhang L, Wei F, Lian Y, Wu Y . Role of tumor microenvironment in tumorigenesis. J Cancer. 2017; 8(5):761-773. PMC: 5381164. DOI: 10.7150/jca.17648. View

Mosmann T . Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2):55-63. DOI: 10.1016/0022-1759(83)90303-4. View

Lemos A, Gomes A, Loureiro J, Brandao P, Palmeira A, Pinto M . Synthesis, Biological Evaluation, and In Silico Studies of Novel Aminated Xanthones as Potential p53-Activating Agents. Molecules. 2019; 24(10). PMC: 6571851. DOI: 10.3390/molecules24101975. View

Chanput W, Mes J, Wichers H . THP-1 cell line: an in vitro cell model for immune modulation approach. Int Immunopharmacol. 2014; 23(1):37-45. DOI: 10.1016/j.intimp.2014.08.002. View

Gabrani R, Jain R, Sharma A, Sarethy I, Dang S, Gupta S . Antiproliferative Effect of Solanum nigrum on Human Leukemic Cell Lines. Indian J Pharm Sci. 2013; 74(5):451-3. PMC: 3660872. DOI: 10.4103/0250-474X.108421. View

Brown J, Recht L, Strober S . The Promise of Targeting Macrophages in Cancer Therapy. Clin Cancer Res. 2017; 23(13):3241-3250. PMC: 5529121. DOI: 10.1158/1078-0432.CCR-16-3122. View

Zhang J, Yan Y, Yang Y, Wang L, Li M, Wang J . High Infiltration of Tumor-Associated Macrophages Influences Poor Prognosis in Human Gastric Cancer Patients, Associates With the Phenomenon of EMT. Medicine (Baltimore). 2016; 95(6):e2636. PMC: 4753880. DOI: 10.1097/MD.0000000000002636. View

10.

Chanput W, Reitsma M, Kleinjans L, Mes J, Savelkoul H, Wichers H . β-Glucans are involved in immune-modulation of THP-1 macrophages. Mol Nutr Food Res. 2012; 56(5):822-33. DOI: 10.1002/mnfr.201100715. View

11.

Tomasini R, Secq V, Pouyet L, Thakur A, Wilhelm M, Nigri J . TAp73 is required for macrophage-mediated innate immunity and the resolution of inflammatory responses. Cell Death Differ. 2012; 20(2):293-301. PMC: 3554333. DOI: 10.1038/cdd.2012.123. View

12.

Dhillon P, Yeole B, Dikshit R, Kurkure A, Bray F . Trends in breast, ovarian and cervical cancer incidence in Mumbai, India over a 30-year period, 1976-2005: an age-period-cohort analysis. Br J Cancer. 2011; 105(5):723-30. PMC: 3188937. DOI: 10.1038/bjc.2011.301. View

13.

Zheng X, Turkowski K, Mora J, Brune B, Seeger W, Weigert A . Redirecting tumor-associated macrophages to become tumoricidal effectors as a novel strategy for cancer therapy. Oncotarget. 2017; 8(29):48436-48452. PMC: 5564660. DOI: 10.18632/oncotarget.17061. View

14.

Imai K, Takeshita A, Hanazawa S . Transforming growth factor-beta inhibits lipopolysaccharide-stimulated expression of inflammatory cytokines in mouse macrophages through downregulation of activation protein 1 and CD14 receptor expression. Infect Immun. 2000; 68(5):2418-23. PMC: 97440. DOI: 10.1128/IAI.68.5.2418-2423.2000. View

15.

Silva V, Cerqueira F, Nazareth N, Medeiros R, Sarmento A, Sousa E . 1,2-Dihydroxyxanthone: Effect on A375-C5 Melanoma Cell Growth Associated with Interference with THP-1 Human Macrophage Activity. Pharmaceuticals (Basel). 2019; 12(2). PMC: 6630936. DOI: 10.3390/ph12020085. View

16.

Guo Q, Jin Z, Yuan Y, Liu R, Xu T, Wei H . New Mechanisms of Tumor-Associated Macrophages on Promoting Tumor Progression: Recent Research Advances and Potential Targets for Tumor Immunotherapy. J Immunol Res. 2016; 2016:9720912. PMC: 5128713. DOI: 10.1155/2016/9720912. View

17.

Dijkman G, Debruyne F . Epidemiology of prostate cancer. Eur Urol. 1996; 30(3):281-95. DOI: 10.1159/000474185. View

18.

Oh Y, Lee H, Jeong M, Rhee M, Mo J, Song E . Role of activating transcription factor 3 on TAp73 stability and apoptosis in paclitaxel-treated cervical cancer cells. Mol Cancer Res. 2008; 6(7):1232-49. PMC: 3783268. DOI: 10.1158/1541-7786.MCR-07-0297. View

19.

Pedro M, Cerqueira F, Sousa M, Nascimento M, Pinto M . Xanthones as inhibitors of growth of human cancer cell lines and their effects on the proliferation of human lymphocytes in vitro. Bioorg Med Chem. 2002; 10(12):3725-30. DOI: 10.1016/s0968-0896(02)00379-6. View

20.

Aras S, Zaidi M . TAMeless traitors: macrophages in cancer progression and metastasis. Br J Cancer. 2017; 117(11):1583-1591. PMC: 5729447. DOI: 10.1038/bjc.2017.356. View