scholarly journals Оценка эффективности противоопухолевого воздействия и индукции апоптоза в клетках карциномы почки человека биологически активными добавками, содержащими ресвератрол, индол-3-карбинол и кордицепин, флуоресцентными методами визуализации

2021 ◽  
Vol 129 (6) ◽  
pp. 727
Author(s):  
Н.В. Полуконова ◽  
Д.С. Исаев ◽  
А.М. Мыльников ◽  
А.Б. Бучарская ◽  
А.В. Полуконова ◽  
...  

We compared the effectiveness of antitumor effects and apoptosis induction on human renal cell carcinoma A498 extracts of cruciferous plant material (indole-3-carbinol), Chinese mushroom (cordycepin), French red wine (resveratrol) at low concentrations after 24 and 48 h using fluorescent methods of imaging apoptosis and necrosis in human tumor cells in vitro . Propidium iodide and acridine orange were used as dyes in the "alive and dead" test, which allowed us to detect the number of dead cells and cells in which apoptosis had started. It was found that indole-3-carbinol at low concentrations (0.0288 and 0.1152 mg/ml) has a pronounced cytotoxic and cytostatic activity against human kidney cancer cells, significantly exceeding the action of resveratrol at the same concentrations. At the same time, cordycepin has no cytotoxic and cytostatic activity at these concentrations. Indole-3-carbinol also has the most pronounced apoptotic activity at concentrations of 0.0144-0.1152 mg/ml, after 48 h the number of kidney cancer cells in apoptosis increases by 6.8-10 times compared to control. It is concluded that indole-3-carbinol is a promising antitumor agent for use in the complex therapy of patients with kidney cancer.

2020 ◽  
Vol 129 (7) ◽  
pp. 964
Author(s):  
А.М. Мыльников ◽  
Н.В. Полуконова ◽  
Д.С. Исаев ◽  
А.А. Дорошенко ◽  
Р.А. Верховский ◽  
...  

Using fluorescence methods for visualizing apoptosis and necrosis in human tumor cells in vitro, we compared the efficacy of antitumor effects on human kidney carcinoma cells A498 flavonoid-containing extracts: Gratiola officinalis and green tea at ultra low concentrations after 24 and 48 h. Fluorescent dyes (propidium iodide and acridine orange) were used in the “living and dead test”, which made it possible to identify the total number of dead cells by necrosis and apoptosis, as well as cells in which apoptosis started, and apoptotic bodies or pycnosis of the nucleus were detected. Avrana extract possessed the most pronounced cytostatic activity 48 h after exposure, reducing the number of cells in the field of view by 1.5 times in comparison with the control. The most pronounced cytotoxic activity was possessed by green tea extract at a concentration of 0.0288 mg / ml, and its severity increased 48 h after exposure. Avran’s extract showed cytotoxic activity at lower concentrations (0.0036 mg / ml).


2020 ◽  
Vol 19 (16) ◽  
pp. 1949-1965 ◽  
Author(s):  
Natalia Szkaradek ◽  
Daniel Sypniewski ◽  
Dorota Żelaszczyk ◽  
Sabina Gałka ◽  
Paulina Borzdziłowska ◽  
...  

Background: Natural plant metabolites and their semisynthetic derivatives have been used for years in cancer therapy. Xanthones are oxygenated heterocyclic compounds produced as secondary metabolites by higher plants, fungi or lichens. Xanthone core may serve as a template in the synthesis of many derivatives that have broad biological activities. Objective: This study synthesized a series of 17 new xanthones, and their anticancer potential was also evaluated. Methods: The anticancer potential was evaluated in vitro using a highly invasive T24 cancer cell line. Direct cytotoxic effects of the xanthones were established by IC50 estimation based on XTT assay. Results: 5 compounds of the total 17 showed significant cytotoxicity toward the studied cancer cultures and were submitted to further detailed analysis, including studies examining their influence on gelatinase A and B expression, as well as on the cancer cells migration and adhesion to an extracellular matrix. These analyses were carried out on five human tumor cell lines: A2780 (ovarian cancer), A549 (lung cancer), HeLa (cervical cancer), Hep G2 (liver cancer), and T24 (urinary bladder cancer). All the compounds, especially 4, showed promising anticancer activity: they exhibited significant cytotoxicity towards all the evaluated cell lines, including MCF-7 breast cancer, and hindered migration-motility activity of cancer cells demonstrating more potent activity than α-mangostin which served as a reference xanthone. Conclusion: These results suggest that our xanthone derivatives may be further analyzed in order to include them in cancer treatment protocols.


2021 ◽  
pp. 096032712199945
Author(s):  
AT Aliyev ◽  
S Ozcan-Sezer ◽  
A Akdemir ◽  
H Gurer-Orhan

Apigenin, a flavonoid, is reported to act as an estrogen receptor (ER) agonist and inhibit aromatase enzyme. However, amentoflavone, a biflavonoid bearing two apigenin molecules, has not been evaluated for its endocrine modulatory effects. Besides, it is highly consumed by young people to build muscles, enhance mood and lose weight. In the present study, apigenin was used as a reference molecule and ER mediated as well as ER-independent estrogenic/antiestrogenic activity of amentoflavone was investigated. Antitumor activity of amentoflavone was also investigated in both ER positive (MCF-7 BUS) and triple-negative (MDA-MB-231) breast cancer cells and its cytotoxicity was evaluated in human breast epithelial cells (MCF-10A). Our data confirmed ER agonist, aromatase inhibitory and cytotoxic effects of apigenin in breast cancer cells, where no ER mediated estrogenic effect and physiologically irrelevant, slight, aromatase inhibition was found for amentoflavone. Although selective cytotoxicity of amentoflavone was found in MCF-7 BUS cells, it does not seem to be an alternative to the present cytotoxic drugs. Therefore, neither an adverse effect, mediated by an estrogenic/antiestrogenic effect of amentoflavone nor a therapeutical benefit would be expected from amentoflavone. Further studies could be performed to investigate its in vivo effects.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lea Miebach ◽  
Eric Freund ◽  
Stefan Horn ◽  
Felix Niessner ◽  
Sanjeev Kumar Sagwal ◽  
...  

AbstractRecent research indicated the potential of cold physical plasma in cancer therapy. The plethora of plasma-derived reactive oxygen and nitrogen species (ROS/RNS) mediate diverse antitumor effects after eliciting oxidative stress in cancer cells. We aimed at exploiting this principle using a newly designed dual-jet neon plasma source (Vjet) to treat colorectal cancer cells. A treatment time-dependent ROS/RNS generation induced oxidation, growth retardation, and cell death within 3D tumor spheroids were found. In TUM-CAM, a semi in vivo model, the Vjet markedly reduced vascularized tumors' growth, but an increase of tumor cell immunogenicity or uptake by dendritic cells was not observed. By comparison, the argon-driven single jet kINPen, known to mediate anticancer effects in vitro, in vivo, and in patients, generated less ROS/RNS and terminal cell death in spheroids. In the TUM-CAM model, however, the kINPen was equivalently effective and induced a stronger expression of immunogenic cancer cell death (ICD) markers, leading to increased phagocytosis of kINPen but not Vjet plasma-treated tumor cells by dendritic cells. Moreover, the Vjet was characterized according to the requirements of the DIN-SPEC 91315. Our results highlight the plasma device-specific action on cancer cells for evaluating optimal discharges for plasma cancer treatment.


Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1028
Author(s):  
Nikolaos Nikoleousakos ◽  
Panagiotis Dalezis ◽  
Aikaterini Polonifi ◽  
Elena G. Geromichalou ◽  
Sofia Sagredou ◽  
...  

We evaluated three newly synthesized B-lactam hybrid homo-aza-steroidal alkylators (ASA-A, ASA-B and ASA-C) for their PARP1/2 inhibition activity and their DNA damaging effect against human ovarian carcinoma cells. These agents are conjugated with an alkylating component (POPA), which also served as a reference molecule (positive control), and were tested against four human ovarian cell lines in vitro (UWB1.289 + BRCA1, UWB1.289, SKOV-3 and OVCAR-3). The studied compounds were thereafter compared to 3-AB, a known PARP inhibitor, as well as to Olaparib, a standard third-generation PARP inhibitor, on a PARP assay investigating their inhibitory potential. Finally, a PARP1 and PARP2 mRNA expression analysis by qRT-PCR was produced in order to measure the absolute and the relative gene expression (in mRNA transcripts) between treated and untreated cells. All the investigated hybrid steroid alkylators and POPA decreased in vitro cell growth differentially, according to the sensitivity and different gene characteristics of each cell line, while ASA-A and ASA-B presented the most significant anticancer activity. Both these compounds induced PARP1/2 enzyme inhibition, DNA damage (alkylation) and upregulation of PARP mRNA expression, for all tested cell lines. However, ASA-C underperformed on average in the above tasks, while the compound ASA-B induced synthetic lethality effects on the ovarian cancer cells. Nevertheless, the overall outcome, leading to a drug-like potential, provides strong evidence toward further evaluation.


Author(s):  
Junhui Yu ◽  
Kui Yang ◽  
Jianbao Zheng ◽  
Wei Zhao ◽  
Xuejun Sun

Abstract The tumor-suppressive role of Farnesoid X receptor (FXR) in colorectal tumorigenesis supports restoring FXR expression as a novel therapeutic strategy. However, the complicated signaling network and tumor heterogeneity hinder the effectiveness of FXR agonists in the clinical setting. These difficulties highlight the importance of identifying drug combinations with potency and specificity to enhance the antitumor effects of FXR agonists. In this study, we found that the β-catenin level affected the antitumor effects of the FXR agonist OCA on colon cancer cells. Mechanistic studies identified a novel FXR/β-catenin complex in colon cancer cells. Furthermore, the depletion of β-catenin expedited FXR nuclear localization and enhanced its occupancy of the SHP promoter and thereby sensitized colon cancer cells to OCA. Furthermore, we utilized a drug combination study and identified that the antiparasitic drug nitazoxanide (NTZ) abrogated β-catenin expression and acted synergistically with OCA in colon cancer cells. The combination of OCA plus NTZ exerts synergistic tumor inhibition in CRC both in vitro and in vivo by cooperatively upregulating SHP expression. In conclusion, our study offers useful evidence for the clinical use of FXR agonists combined with β-catenin inhibitors in combating CRC.


2020 ◽  
Vol 118 ◽  
pp. 104846
Author(s):  
Qingwei Zheng ◽  
Jing Sun ◽  
Wenli Li ◽  
Shuangnan Li ◽  
Kai Zhang

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