Methanolic extract of Teucrium Polium L potentiates the cytotoxic and apoptotic effects of anticancer drugs of vincristine, vinblastine and doxorubicin against a panel of cancerous cell lines

A growing body of evidence indicates that specific phytochemicals can increase an efficacy of cancer chemotherapy. Aim: To evaluate promoting effect of the methanolic extract of Teucrium Polium (Me-TP) on cytotoxic and apoptotic activity of anticancer drugs of vinblastine, vincristine and doxorubicin in vitro. Methods: Skmel-3, Saos-2, SW480, MCF-7, KB, EJ and A431 cell lines were used. Cytotoxicity was determined by MTT assay and colony formation assay. The nature of interactions was analyzed by combination index (CI) method. Apoptotic cells were assessed by DAPI staining. Results: The vincristine/Me-TP, vinblastine/Me-TP and doxorubicin/Me-TP combinations showed a strong synergistic effect in the cell growth inhibition (0.13 80%) compared to effect of individual drugs (0–3%). At the additional experiments, Me-TP reduced marginally to significantly the cytotoxic effects of vincristine and vinblastine toward the human fibroblasts (p < 0.05 to 0.001). Conclusions: The present study suggests that Me-TP has the potential to be an effective and safe chemosensitizer agent for cancer therapy.Исследования последних лет показали, что некоторые фитопрепараты могут усиливать эффект химиотерапии. Цель: оценить in vitro влияние метанольного экстракта Teucrium Polium (Me-TP) на цитотоксичность и апоптоз, индуцируемые противоопухолевыми препаратами винбластином, винкристином и доксорубицином. Методы: в работе использованы клеточные линии Skmel-3, Saos-2, SW480, MCF-7, KB, EJ и A431. Цитотоксичность определяли с помощью MTT теста и реакции колониеобразования. Характер воздействия препаратов изучали с помощью метода комбинированного индекса (CI поптотические клетки выявляли окрашиванием DAPI. Результаты: для комбинаций винкристин/Me-TP, винбластин/Me-TP и доксорубицин/Me-TP было выявлено сильное синергичное воздействие на торможение клеточного роста (0,13 < CI < 0,36). Аналогичные результаты получены при определении способности клеток к колониеобразованию. Более того, комбинации винкристин/Me-TP и винбластин/Me-TP вызывали выраженный апоптоз клеток (> 80%) по сравнению с химиопрепаратами без Me-TP (0–3%). Показано также, что Me-TP снижал цитотоксическое воздействие (от минимальной до значительной степени) винкристина и винбластина на фибробласты человека (p < 0,05 до 0,001). Выводы: Me-TP можно рассматривать как возможный эффективный и безопасный химиосенсибилизирующий препарат для химиотерапии

In Vitro Cytotoxicity Evaluation of Sixteen New N-Piperazinyl Quinolone Derivatives Against A Panel Of Tumor Cell Lines

Abstract: Introduction: Fluoroquinolones are potent inhibitors of bacterial topoisomerase II. They can also inhibit eukaryotic topoisomerase, and may confer antitumoral properties. Method: In this study the antitumoral activity of a new series of N-substituted piperazinyl- fluoroquinolones against a panel of human tumor cell lines was determined by MTT assays. Results: Among the tested compounds N-[2- (5-bromo-2-thienyl)-2-oxoethyl ] (C1,N1,E1), N-[ 2- (5-bromo-2-thienyl)-2-(hydroxyimino) ethyl]( C2,N2,E2) and N-[2-(5-bromo-2-thienyl)-2-(phenylmethoxyimino) ethyl] (C3,N3,E3) piperazinyl quinolones exhibited the most cytotoxic activities (mean IC50s = 2.5 to 3 μg/ml), comparable to that of the Etoposide (mean IC50= 1.7μg/ml). Replacement of the 5- bromo-2-thienyl with 4- fluorophenyl or 2,6- difluorophenyl rings leads to variable inhibition activity. The quinolone activity was enhanced by the presence of a chlorine and two fluorine atoms at the benzyl and phenyl groups, especially against ACHN renal adenocarcinoma cell line. Conclusion: These data suggest that these series of quinolones provide good models for the further design of potent antitumor compounds. Keywords: Cytotoxicity, Fluoroquinolone, MTT- assay, Etoposid

In vitro cytotoxicity and apoptotic inducing activity of the synthesized 4-aryl-4H-chromenes derivatives against human cancer cell lines

&quot;n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: 4-Aryl-4H-chromenes are novel anticancer agents which induce apoptosis in cancer cells. These compounds were found to induce apoptosis by targeting the tubulin/microtubule system in cell proliferation process. The aim of this study was to report cyototoxic and apoptosis inducing activities of a new series of synthesized 4-aryl-4H-chromenes compounds.&quot;n&quot;n Methods: The in vitro cytotoxic activity of the synthesized 4-aryl-4H-chromenes was investigated against a paned of human cancer cell lines including MCF-7 (breast carcinoma), A549 (lung carcinoma), HEPG-2 (liver carcinoma), SW-480 (colon adenocarcinoma), U87-MG (glioblastoma), 1321N1 (astrocytoma), and DAOY (medulloblastoma). The percentage of growth inhibitory activity was evaluated using MTT colorimetric assay versus controls not treated with test derivatives. The data for etoposide, a well known anticancer drug, was included for comparison. For each compound, the 50% inhibitory concentration (IC50) were determined. Apoptosis inducing activity were assessed by DAPI staining.&quot;n&quot;n Results: Preliminary screening showed that those chromenes analogs bearing phenyl-isoxazole-3-yl substitution or the derivatives containing methoxyphenyl in chromene ring exhibited cytotoxic and apoptotic inducing activity comparable with or even superior than the reference drug, etoposide. The compounds without this type of substitution have lower activity. &quot;n&quot;nConclusions: Replacement of 3, 4, 5-trimethoxyphenyl group with thiazol ring in the synthesized derivatives reduced the cytotoxic activity. However, the derivatives with phenyl-isoxazole analogue showed potent cytotoxic and apoptotic inducing activity

Synthesis and anti-Helicobacter pylori activity of 5-(nitroaryl)-1,3,4-thiadiazoles with certain sulfur containing alkyl side chain

A series of 5-(nitroaryl)-1,3,4-thiadiazoles bearing certain sulfur containing alkyl side chain similar to pendent residue in tinidazole molecule were synthesized and evaluated against Helicobacter pylori using disk diffusion method. The synthesized compounds were also evaluated for their antibacterial, antifungal and cytotoxic effects. Study of the structure-activity relationships of this series of compounds indicated that both the structure of the nitroaryl unit and the pendent group on 2-position of 1,3,4-thiadiazole ring dramatically impact the anti-H. pylori activity. While compound 7a containing 2-2-(ethylsulfonyl)ethylthio-side chain from nitrothiophene series was the most potent compound tested against clinical isolates of H. pylori, however, nitroimidazoles 6c and 7c were found to be more promising compounds because of their respectable anti-H. pylori activity besides less cytotoxic effects. © 2008 Elsevier Ltd. All rights reserved

The frequency of p53, Ki67, CD99 and Fli-1 protein expression in paraffin-embedded tissue blocks in Ewing’s sarcoma

&quot;n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Ewing sarcoma family tumors (ESFTs) are among the most malignant tumors in children and young adults. ESFTs include Ewing sarcoma (ES) and peripheral primitive neuroectodermal tumors (pPNETs). As there seemed to be few studies on the molecular biology of ESFTs, we investigated the frequency of CD99, Ki67, p53 and Fli-1 protein expression in 15 Iranian patients with ESFTs. In addition, the correlation between expression rate of these proteins and various clinical factors, including age, sex and survival was computed.&quot;n&quot;nMethods: The expression of the aforesaid proteins was studied by immunohisto-chemistry in formalin-fixed and paraffin-embedded blocks of 15 ESFTs specimens. Stained sections were classified according to the percentage of stained tumor cells.&quot;n&quot;nResults: The results showed the membrane expression of CD99 protein in all of the specimens. The nuclear expression of Fli-1 protein was observed in 86.7% and the over-expression of p53 nuclear protein was seen in 53.3% of the specimens. The expression rate of Ki67 protein was 60%. Although a significant correlation was not shown between the expression levels of Ki67, p53 or Fli-1 proteins with age, sex or survival of the patients, there was a significant correlation between expression levels of p53 and Ki67 proteins (P=0.003).&quot;n&quot;nConclusion: The results underline the role of p53 and Ki67 proteins in the development and progression of ESFTs and suggest the simultaneous immunohistochemical staining of Fli-1 and CD99 proteins for the diagnosis of ESFTs

Five-year relative survival and determinants of excess mortality in patients with head and neck and thyroid cancers: A population-based study from Golestan province, Northern Iran

Background: We aimed to assess relative survival (RS) and determinants of excess mortality rate in patients with head and neck squamous cell carcinomas (HNSCC) and thyroid cancer in Golestan province, Northern Iran. Methods: We recruited new primary HNSCC and thyroid cancer cases from Golestan, 2006�2016. Five-year age-standardized RS with their 95 confidence intervals (CIs) were calculated. The relationships between different variables with excess mortality rates were assessed by estimating adjusted excess hazard ratios (aEHRs) with their 95 CIs. Results: Overall, 718 cases of HNSCC and 386 thyroid cancer cases were enrolled. Five-year age-standardized RS (95 CI) were 36 (31�41) and 61 (52�69) in HNSCC and thyroid cancer patients, respectively. There were significant relationship between excess mortality rates in HNSCC patients with metastasis (aEHR= 3.31; 95CI: 2.26�4.84), treatment type (4.19; 2.54�6.91, for no treatment as compared to receiving both surgery and chemoradiotherapy), age (2.16; 1.57�2.96, for older age group) and smoking (2.00; 1.45�2.75, for smokers as compared to non-smokers). Determinant of the excess mortality in thyroid cancer patients included metastasis (19.65; 8.08�47.79), tumor morphology (12.27; 4.62�32.58, for anaplastic cancer as compared to papillary cancer), treatment type (8.95, 4.13�19.4, for no treatment as compared to receiving both surgery and iodine therapy) and age (2.31; 1.17�4.54, for older age group). Conclusion: Our findings suggested low RS for thyroid cancer in our population, while the estimates for HNSCC were comparable with other population. Metastasis, treatment type and age were determinants of mortality both in thyroid and HNSCC patients. © 2022 Elsevier Lt