δ-Tocopherol Enhances Docetaxel-Induced Growth Inhibition and Apoptosis in Ovarian Cancer SKOV3 Cells

Docetaxel is the first-line chemotherapeutic drug for ovarian cancer. However, its clinical use is limited owing to its serious side effects. Therefore, it is of great clinical significance to enhance the efficacy of docetaxel at lower doses in a less-toxic manner. In this study, we investigated whether δ-tocopherol could enhance the anti-tumor effects of docetaxel on ovarian cancer SKOV3 cells in vitro. For docetaxel and δ-tocopherol, IC50 values of 1.89 nM and 11.41 µM, respectively, were obtained, in SKOV3 cells. The combination of δ-tocopherol and docetaxel had a synergistic cell growth inhibition effect, with lower cell viability and more cell arrest at the S phase compared to either δ-tocopherol or docetaxel alone. In addition, the combination of δ-tocopherol and docetaxel had a synergistic cell apoptosis induction effect, with more apoptotic cells and reduced anti-apoptotic protein expression compared to either δ-tocopherol or docetaxel alone. Furthermore, we identified 3 hoursub genes (CAT, EP300, CREBBP), which predicted the prognosis of ovarian cancer, which correlated with δ-tocopherol and docetaxel. In conclusion, the combination of δ-tocopherol and docetaxel presented synergistic cell growth inhibition and cell apoptosis induction effects in SKOV3 cells at a low dose, which suggesting that δ-tocopherol could improve the serious side effects of docetaxel.

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Effect of 5-fluoro-2′-deoxycytidine (FdCyd) on p16INK4a, p14ARF, p15INK4b, and DNA methyltransferase 1, 3a, and 3b Genes Expression, Apoptosis Induction, and Cell Growth Inhibition in Pancreatic Cancer AsPC-1 and Hepatocellular Carcinoma LCL-PI 11 Cell Li

Iranian Journal of Pediatric Hematology & Oncology ◽

10.18502/ijpho.v11i1.5000 ◽

2020 ◽

Author(s):

Masumeh Sanaei ◽

Fraidoon Kavoosi

Keyword(s):

Cell Growth ◽

Growth Inhibition ◽

Cell Apoptosis ◽

Dna Methyltransferase ◽

Dna Methyltransferase 1 ◽

Dependent Manner ◽

Apoptosis Induction ◽

Cell Growth Inhibition ◽

Genes Expression ◽

Methyltransferase 1

Background: Aberrant DNA methylation of the promoter region is one of the most epigenetic changes in numerous cancers. DNA methyltransferase inhibitors (DNMTIs) can revert DNA hypermethylation in tumor suppressor genes (TSGs). The present study was designed to investigate the effect of 5-fluoro-2′-deoxycytidine (FdCyd) on p16INK4a, p14ARF, p15INK4b, and DNA methyltransferase 1, 3a, and 3b genes expression, apoptosis induction, cell growth inhibition in pancreatic cancer AsPC-1 and hepatocellular carcinoma LCL-PI 11 cell lines. Materials and Methods: The cells were treated with FdCyd at different periods. Then, the MTT assay, cell apoptosis assay, and qRT-PCR were done to determine cell viability, cell apoptosis, and the relative gene expression level respectively. Results: The FdCyd decreased DNA methyltransferase 1, 3a, and 3b and increased p16INK4a, p14ARF, and p15INK4b genes expression significantly (P<0.001). Besides, LCL-PI 11 cell was more sensitive to FdCyd in comparison to AsPC-1 cell. FdCyd induced significant cell growth inhibition with a dose- and time-dependent manner (P<0.001). The IC50 value of FdCyd was obtained with approximately 1μM. Further, FdCyd induced cell apoptosis significantly as a time-dependent manner. The number of apoptotic cells was significantly increased in all groups. The percentage of apoptotic cells after 24 and 48 h were 13.86 and 29.6 % in AsPC-1 and 21.04 and 41.52 % in LCL-PI 11 cell line respectively (P<0.001). Conclusion: The FdCyd can reactivate the p16INK4a, p14ARF, and p15INK4b through inhibition of DNA methyltransferase 1, 3a, and 3b gene expression.

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In VivoAnticancer Activity ofBasella albaLeaf and Seed Extracts against Ehrlich's Ascites Carcinoma (EAC) Cell Line

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/1537896 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Md. Shihabul Islam ◽

Md. Sifat Rahi ◽

Chowdhury Arif Jahangir ◽

Md Habibur Rahman ◽

Israt Jerin ◽

...

Keyword(s):

Side Effects ◽

Cell Growth ◽

Growth Inhibition ◽

Cell Line ◽

Seed Extract ◽

Morphological Alteration ◽

Pcr Analysis ◽

Apoptosis Induction ◽

Cell Growth Inhibition ◽

Seed Extracts

Cancer is a class of diseases characterized by uncontrolled cell growth. The current treatment options of cancer are radiotherapy, chemotherapy, hormone therapy, and surgery, where all of them have unpleasant side effects. Due to their adverse side effects, it is challenging to develop new drug for cancer treatment. Hence, the scientists are trying to seek for noble compounds from natural sources to treat cancer. Therefore, in the present investigation, a widely consumable vegetableBasella albawas subjected to evaluate its antiproliferative effect along with molecular signaling of apoptosis in Ehrlich ascites carcinoma (EAC) cell line. Cell growth inhibition was determined by haemocytometer whereas apoptosis of cancer cells were studied by florescence microscope using Hoechst-33342 stain and result was supported by DNA fragmentation and certain cancer related genes expression through PCR analysis.B. albaleaf and seed extract exhibit a considerable scavenging activity in comparison to a standard antioxidant BHT. Moreover, the leaf and seed extracts were able to agglutinate 2% RBC of goat blood at minimum 12.5μg/ml and 50.0μg/ml concentration, respectively. A significant cytotoxic activity was also found in both leaf and seed extract. In haemocytometic observation, the leaf and seed extracts exhibit about 62.54±2.41% and 53.96±2.34% cell growth inhibition, respectively, whereas standard anticancer drug Bleomycin showed 79.43±1.92% growth inhibition. Morphological alteration under fluorescence microscope showed nuclear condensation and fragmentation which is the sign of apoptosis. Apoptosis induction was also confirmed by DNA laddering in leaf and seed treated EAC cells. Upregulation of the tumor suppressor gene P53and downregulation of antiapoptotic gene Bcl-2 enumerate apoptosis induction. Therefore, current study manifested that leaf and seed extracts ofB. albahave antiproliferative activity against EAC cell line and can be a potent source of anticancer agents to treat cancer.

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Effect of β-carotene-rich tomato lycopene β-cyclase (tlcy-b) on cell growth inhibition in HT-29 colon adenocarcinoma cells

British Journal Of Nutrition ◽

10.1017/s0007114508169902 ◽

2008 ◽

Vol 102 (2) ◽

pp. 207-214 ◽

Cited By ~ 15

Author(s):

Paola Palozza ◽

Diana Bellovino ◽

Rossella Simone ◽

Alma Boninsegna ◽

Francesco Cellini ◽

...

Keyword(s):

Cell Growth ◽

Growth Inhibition ◽

Colon Adenocarcinoma ◽

Human Colon ◽

Cell Growth Inhibition ◽

Adenocarcinoma Cells ◽

Ht 29 ◽

Colon Adenocarcinoma Cells ◽

Β Carotene

Lycopene β-cyclase (tlcy-b) tomatoes, obtained by modulating carotenogenesis via genetic engineering, contain a large amount of β-carotene, as clearly visible by their intense orange colour. In the present study we have subjected tlcy-b tomatoes to an in vitro simulated digestion and analysed the effects of digestate on cell proliferation. To this aim we used HT-29 human colon adenocarcinoma cells, grown in monolayers, as a model. Digested tomatoes were diluted (20 ml, 50 ml and 100 ml/l) in culture medium and added to the cells for different incubation times (24 h, 48 h and 72 h). Inhibition of cell growth by tomato digestate was dose-dependent and resulted from an arrest of cell cycle progression at the G0/G1 and G2/M phase and by apoptosis induction. A down-regulation of cyclin D1, Bcl-2 and Bcl-xl expression was observed. We also found that heat treatment of samples before digestion enhanced β-carotene release and therefore cell growth inhibition. To induce with purified β-carotene solubilised in tetrahydrofuran the same cell growth inhibition obtained with the tomato digestate, a higher amount of the carotenoid was necessary, suggesting that β-carotene micellarised during digestion is utilised more efficiently by the cells, but also that other tomato molecules, reasonably made available during digestion, may be present and cooperate with β-carotene in promoting cell growth arrest.

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A Facile Synthesis of 9-Deaza Analogue of Olomoucine

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc20030779 ◽

2003 ◽

Vol 68 (4) ◽

pp. 779-791 ◽

Cited By ~ 7

Author(s):

Petr Čapek ◽

Miroslav Otmar ◽

Milena Masojídková ◽

Ivan Votruba ◽

Antonín Holý

Keyword(s):

Cell Growth ◽

Growth Inhibition ◽

Cell Lines ◽

Alkaline Solution ◽

Catalytic Hydrogenation ◽

Cell Growth Inhibition ◽

Facile Synthesis ◽

Hydroxymethyl Group ◽

Chloro Derivative

Heating of 6-(benzylamino)-2-chloro-9-deazapurine (3) with ethanolamine afforded 6-(benzylamino)-2-[(2-hydroxyethyl)amino]-9-deazapurine (8). Its treatment with formaldehyde in alkaline solution, after protection of the OH group with DMTr, led to hydroxymethylation at position 9. Conversion of the hydroxymethyl group to methyl was performed by catalytic hydrogenation under simultaneous deprotection, which resulted in the formation of the 9-deaza analogue 1 of olomoucine. Compound 1 does not exhibit any significant in vitro cell growth inhibition of CCRF-CEM, HeLa and L-1210 cell lines. Cytostatic activity was found in 6-(benzylamino)-9-deazapurine (2) and its 2-chloro derivative 3 in CCRF-CEM cells with IC50 13.3 and 15.8 μM, respectively.

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TRIAP1 Inhibition Activates the Cytochrome c/Apaf-1/Caspase-9 Signaling Pathway to Enhance Human Ovarian Cancer Sensitivity to Cisplatin

Chemotherapy ◽

10.1159/000501633 ◽

2019 ◽

Vol 64 (3) ◽

pp. 119-128 ◽

Cited By ~ 1

Author(s):

Tian-Mei Zhang

Keyword(s):

Ovarian Cancer ◽

Nude Mice ◽

Cell Apoptosis ◽

Caspase 9 ◽

Ovarian Carcinoma Cell Line ◽

Skov3 Cells ◽

Cyt C ◽

Sirna Group

Objective: To investigate whether TRIAP1inhibition affects the ovarian cancer cell resistance to cisplatin (DDP) via the Cyt c/Apaf-1/caspase-9 pathway by in vitro and in vivo experiments. Methods: CCK8 assay was performed to find out how treatment with both TRIAP1 siRNA and DDP affects the cell viability of SKOV3 cells and DDP-resistant human ovarian carcinoma cell line SKOV3/DDP. SKOV3/DDP cells were transfected with control siRNA or TRIAP1 siRNA before 24 h of treatment with DDP (5 μg/mL). Flow cytometry was employed to detect cell apoptosis and Western blot to examine the expressions of Cyt c/Apaf-1/caspase-9 pathway-related proteins. SKOV3/DDP cells transfected with control siRNA or TRIAP1 siRNA were subcutaneously injected into BALB/c-nu/nu nude mice followed by the intraperitoneal injection of DDP (4 mg/kg). Cyt c/Apaf-1/caspase-9 pathway in transplanted tumors was detected by immunohistochemistry. Results: TRIAP1 expression declined in SKOV3 cells when compared with SKOV3/DDP cells. The proliferation rate was lower in SKOV3/DDP cells transfected with TRIAP1 siRNA combined with treatment of DDP (1, 2, 4, 6, 8, 16, 32 μg/mL) than in those transfected with control siRNA. Moreover, the TRIAP1 siRNA group had an increased SKOV3/DDP cell apoptosis rate with the activation of the Cyt c/Apaf-1/caspase-9 pathway. During DDP treatment, nude mice in TRIAP1 siRNA group had slower growth and smaller size of transplanted tumor than those in control siRNA group, with increased expression of Cyt c, Apaf-1, and caspase-9. Conclusion: TRIAP1 inhibition may enhance the sensitivity of SKOV3/DDP cells to cisplatin via activation of the Cyt c/Apaf-1/caspase-9 pathway.

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