Investigation of Anticancer Properties of Monoterpene-Aminopyrimidine Hybrids on A2780 Ovarian Cancer Cells

被引:4
作者
Nagy, Viktoria [1 ]
Mounir, Raji [2 ]
Szebeni, Gabor J. [3 ]
Szakonyi, Zsolt [2 ,4 ]
Gemes, Nikolett [3 ]
Minorics, Renata [1 ]
German, Peter [1 ]
Zupko, Istvan [1 ,4 ]
机构
[1] Univ Szeged, Inst Pharmacodynam & Biopharm, H-6720 Szeged, Hungary
[2] Univ Szeged, Inst Pharmaceut Chem, H-6720 Szeged, Hungary
[3] Eotvos Lorand Res Network Biol Res Ctr, Inst Genet, Lab Funct Genom, H-6726 Szeged, Hungary
[4] Univ Szeged, Interdisciplinary Ctr Nat Prod, H-6720 Szeged, Hungary
关键词
monoterpene; aminoalcohol; antiproliferative; G2; M arrest; antimetastatic; ovarian cancer; CYCLE ARREST; APOPTOSIS; MIGRATION; GROWTH;
D O I
10.3390/ijms241310581
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The present study aimed to characterize the antiproliferative and antimetastatic properties of two recently synthesized monoterpene-aminopyrimidine hybrids (1 and 2) on A2780 ovary cancer cells. Both agents exerted a more pronounced cell growth inhibitory action than the reference agent cisplatin, as determined by the MTT assay. Tumor selectivity was assessed using non-cancerous fibroblast cells. Hybrids 1 and 2 induced changes in cell morphology and membrane integrity in A2780 cells, as evidenced by Hoechst 33258-propidium iodide fluorescent staining. Cell cycle analysis by flow cytometry revealed substantial changes in the distribution of A2780 ovarian cancer cells, with an increased rate in the subG1 and G2/M phases, at the expense of the G1 cell population. Moreover, the tested molecules accelerated tubulin polymerization in a cell-free in vitro system. The antimetastatic properties of both tested compounds were investigated by wound healing and Boyden chamber assays after 24 and 48 h of incubation. Treatment with 1 and 2 resulted in time- and concentration-dependent inhibition of migration and invasion of A2780 cancer cells. These results support that the tested agents may be worth of further investigation as promising anticancer drug candidates.
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页数:17
相关论文
共 34 条
[1]   The Cancer Microenvironment: Mechanical Challenges of the Metastatic Cascade [J].
Amos, Sebastian E. ;
Choi, Yu Suk .
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, 2021, 9
[2]   Antiproliferative Activity of (-)-Isopulegol-based 1,3-Oxazine, 1,3-Thiazine and 2,4-Diaminopyrimidine Derivatives [J].
Bamou, Fatima Z. ;
Le, Tam M. ;
Tayeb, Bizhar A. ;
Tahaei, Seyyed A. S. ;
Minorics, Renata ;
Zupko, Istvan ;
Szakonyi, Zsolt .
CHEMISTRYOPEN, 2022, 11 (10)
[3]   The carboxyl tail of Cx43 augments p38 mediated cell migration in a gap junction-independent manner [J].
Behrens, Juliane ;
Kameritsch, Petra ;
Wallner, Stefan ;
Pohl, Ulrich ;
Pogoda, Kristin .
EUROPEAN JOURNAL OF CELL BIOLOGY, 2010, 89 (11) :828-838
[4]   Ovarian Cancer Biomarkers: Moving Forward in Early Detection [J].
Bonifacio, Vasco D. B. .
TUMOR MICROENVIRONMENT: THE MAIN DRIVER OF METABOLIC ADAPTATION, 2020, 1219 :355-363
[5]   Mechanism of antiproliferative action of a new D-secoestrone-triazole derivative in cervical cancer cells and its effect on cancer cell motility [J].
Bozsity, Noemi ;
Minorics, Renata ;
Szabo, Johanna ;
Mernyak, Erzsebet ;
Schneider, Gyula ;
Wolfling, Janos ;
Wang, Hui-Chun ;
Wu, Chin-Chung ;
Ocsovszki, Imre ;
Zupko, Istvan .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2017, 165 :247-257
[6]  
Bray F, 2018, CA-CANCER J CLIN, V68, P394, DOI [10.3322/caac.21492, 10.3322/caac.21609]
[7]  
Chen Hong-Chen, 2005, Methods Mol Biol, V294, P15
[8]   Discovery of isopenicin A, a meroterpenoid as a novel inhibitor of tubulin polymerization [J].
Chen, Lin ;
Fan, Dong-Mei ;
Tang, Jian-Wei ;
An, Tao ;
Li, Xue ;
Kong, Ling-Mei ;
Puno, Pema-Tenzin ;
Li, Yan .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2020, 525 (02) :303-307
[9]   Nature: a vital source of leads for anticancer drug development [J].
Cragg, G. M. ;
Newman, D. J. .
PHYTOCHEMISTRY REVIEWS, 2009, 8 (02) :313-331
[10]  
Demain AL, 2005, NATURAL PRODUCTS: DRUG DISCOVERY AND THERAPEUTIC MEDICINE, P3, DOI 10.1007/978-1-59259-976-9_1