Synthesis of New Hydrazone Derivatives and Evaluation of their Efficacy as Proliferation Inhibitors in Human Cancer Cells

2019 ◽  
Vol 15 (8) ◽  
pp. 903-910 ◽  
Author(s):  
Piotr Świątek ◽  
Jolanta Saczko ◽  
Nina Rembiałkowska ◽  
Julita Kulbacka
Keyword(s):  
Cancer Cells ◽  
Anticancer Agents ◽  
Human Cancer ◽  
Anticancer Activities ◽  
Human Cancer Cells ◽  
Viability Assay ◽  
Resistant Phenotype ◽  
Potent Inhibition ◽  
Drug Resistant Phenotype ◽  
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Background: Hydrazine-hydrazones represent a group of bioactive compounds that display antibacterial, anti-inflammatory, antiviral or anticancer activities. Methods: The group of new derivatives was evaluated by the viability assay in human cancer and normal cells. Results: The dimethylpyridine hydrazones showed potent inhibition of cell proliferation of breast, colon cancer cells, human melanoma and glioblastoma. Compound 12 inhibited proliferation of cancer cells exhibiting a drug-resistant phenotype (MCF-7/DX and LoVoDX) at low millimolar concentrations. Whereas, antimelanoma activity was revealed by Compounds 2, 4, 7 and 12. Conclusion: The present results highlighted newly synthetized hydrazine derivatives an excellent base for the design of new anticancer agents and resistance inhibitors.

scholarly journals Effect of Calomelanone, a Dihydrochalcone Analogue, on Human Cancer Apoptosis/Regulated Cell Death in an In Vitro Model

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Wasitta Rachakhom ◽  
Ratana Banjerdpongchai
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Hepg2 Cells ◽  
Cytotoxic Effect ◽  
Human Cancer ◽  
Autophagic Flux ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Human Cancer Cells ◽  
Regulated Cell Death

Calomelanone, 2 ′ ,6 ′ -dihydroxy-4,4 ′ -dimethoxydihydrochalcone, possesses anticancer activities. This study was conducted to investigate the cytotoxic effect of calomelanone, a dihydrochalcone analogue, on human cancer cells and its associated mechanisms. The cytotoxic effect of calomelanone was measured by MTT assay. Annexin V-FITC/propidium iodide and DiOC6 staining that employed flow cytometry were used to determine the mode of cell death and reduction of mitochondrial transmembrane potential (MTP), respectively. Caspase activities were measured using specific substrates and colorimetric analysis. The expression levels of Bcl-2 family proteins were determined by immunoblotting. Reactive oxygen species were also measured using 2 ′ ,7 ′ -dihydrodichlorofluorescein diacetate and dihydroethidium (fluorescence dyes). Calomelanone was found to be toxic towards various human cancer cells, including acute promyelocytic HL-60 and monocytic leukemic U937 cells, in a dose-dependent manner at 24 h and human hepatocellular HepG2 cells at 48 h. However, the proliferation of HepG2 cells increased at 24 h. Calomelanone was found to induce apoptosis in HL-60 and U937 at 24 h and HepG2 apoptosis at 48 h via the intrinsic pathway by inducing MTP disruption. This compound also induced caspase-3, caspase-8, and caspase-9 activities. Calomelanone upregulated proapoptotic Bax and Bak and downregulated antiapoptotic Bcl-xL proteins in HepG2 cells. Moreover, signaling was also associated with oxidative stress in HepG2 cells. Calomelanone induced autophagy at 24 h of treatment, which was evidenced by staining with monodansylcadaverine (MDC) to represent autophagic flux. This was associated with a decrease of Akt (survival pathway) and an upregulation of Atg5 (the marker of autophagy). Thus, calomelanone induced apoptosis/regulated cell death in HL-60, U937, and HepG2 cells. However, it also induced autophagy in HepG2 depending on duration, dose, and type of cells. Thus, calomelanone could be used as a potential anticancer agent for cancer treatment. Nevertheless, acute and chronic toxicity should be further investigated in animals before conducting investigations in human patients.

scholarly journals Inhibition of NADPH Oxidases Activity by Diphenyleneiodonium Chloride as a Mechanism of Senescence Induction in Human Cancer Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1248
Author(s):  
Katarzyna Piszczatowska ◽  
Dorota Przybylska ◽  
Ewa Sikora ◽  
Grażyna Mosieniak
Keyword(s):  
Cancer Cells ◽  
Therapeutic Potential ◽  
Human Cancer ◽  
Cell Metabolism ◽  
Human Colon ◽  
Nadph Oxidases ◽  
Human Colon Cancer ◽  
Inhibition Of Proliferation ◽  
Human Cancer Cells ◽  
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NADPH oxidases (NOX) are commonly expressed ROS-producing enzymes that participate in the regulation of many signaling pathways, which influence cell metabolism, survival, and proliferation. Due to their high expression in several different types of cancer it was postulated that NOX promote tumor progression, growth, and survival. Thus, the inhibition of NOX activity was considered to have therapeutic potential. One of the possible outcomes of anticancer therapy, which has recently gained much interest, is cancer cell senescence. The induction of senescence leads to prolonged inhibition of proliferation and contributes to tumor growth restriction. The aim of our studies was to investigate the influence of low, non-toxic doses of diphenyleneiodonium chloride (DPI), a potent inhibitor of flavoenzymes including NADPH oxidases, on p53-proficient and p53-deficient HCT116 human colon cancer cells and MCF-7 breast cancer cells. We demonstrated that the temporal treatment of HCT116 and MCF-7 cancer cells (both p53 wild-type) with DPI caused induction of senescence, that was correlated with decreased level of ROS and upregulation of p53/p21 proteins. On the contrary, in the case of p53−/− HCT116 cells, apoptosis was shown to be the prevailing effect of DPI treatment. Thus, our studies provided a proof that inhibiting ROS production, and by this means influencing ROS sensitive pathways, remains an alternative strategy to facilitate so called therapy-induced senescence in cancers.

scholarly journals Maytenus disticha Extract and an Isolated β-Dihydroagarofuran Induce Mitochondrial Depolarization and Apoptosis in Human Cancer Cells by Increasing Mitochondrial Reactive Oxygen Species

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 377
Author(s):  
Iván González-Chavarría ◽  
Felix Duprat ◽  
Francisco J. Roa ◽  
Nery Jara ◽  
Jorge R. Toledo ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Cancer Cells ◽  
Human Cancer ◽  
Ros Generation ◽  
Active Components ◽  
Total Extract ◽  
Human Cancer Cells ◽  
Mitochondrial Superoxide ◽  
Mitochondrial Membrane Depolarization ◽  
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Maytenus disticha (Hook F.), belonging to the Celastraceae family, is an evergreen shrub, native of the central southern mountains of Chile. Previous studies demonstrated that the total extract of M. disticha (MD) has an acetylcholinesterase inhibitory activity along with growth regulatory and insecticidal activities. β-Dihydroagarofurans sesquiterpenes are the most active components in the plant. However, its activity in cancer has not been analyzed yet. Here, we demonstrate that MD has a cytotoxic activity on breast (MCF-7), lung (PC9), and prostate (C4-2B) human cancer cells with an IC50 (µg/mL) of 40, 4.7, and 5 µg/mL, respectively, an increasing Bax/Bcl2 ratio, and inducing a mitochondrial membrane depolarization. The β-dihydroagarofuran-type sesquiterpene (MD-6), dihydromyricetin (MD-9), and dihydromyricetin-3-O-β-glucoside (MD-10) were isolated as the major compounds from MD extracts. From these compounds, only MD-6 showed cytotoxic activity on MCF-7, PC9, and C4-2B with an IC50 of 31.02, 17.58, and 42.19 µM, respectively. Furthermore, the MD-6 increases cell ROS generation, and MD and MD-6 induce a mitochondrial superoxide generation and apoptosis on MCF-7, PC9, and C4-2B, which suggests that the cytotoxic effect of MD is mediated in part by the β-dihydroagarofuran-type that induces apoptosis by a mitochondrial dysfunction.

scholarly journals Heat Stress-Induced Multiple Multipolar Divisions of Human Cancer Cells

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 888 ◽  
Author(s):  
Chen ◽  
Liu ◽  
Huang ◽  
Li ◽  
Zhao ◽  
...  
Keyword(s):  
Heat Stress ◽  
Cancer Cells ◽  
Cell Fusion ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Daughter Cells ◽  
Mitotic Slippage ◽  
Polyploid Cells ◽  
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Multipolar divisions of heated cells has long been thought to stem from centrosome aberrations of cells directly caused by heat stress. In this paper, through long-term live-cell imaging, we provide direct cellular evidences to demonstrate that heat stress can promote multiple multipolar divisions of MGC-803 and MCF-7 cells. Our results show that, besides facilitating centrosome aberration, polyploidy induced by heat stress is another mechanism that causes multipolar cell divisions, in which polyploid cancer cells engendered by mitotic slippage, cytokinesis failure, and cell fusion. Furthermore, we also find that the fates of theses polyploid cells depend on their origins, in the sense that the polyploid cells generated by mitotic slippage experience bipolar divisions with a higher rate than multipolar divisions, while those polyploid cells induced by both cytokinesis failure and cell fusion have a higher frequency of multipolar divisions compared with bipolar divisions. This work indicates that heat stress-induced multiple multipolar divisions of cancer cells usually produce aneuploid daughter cells, and might lead to genetically unstable cancer cells and facilitate tumor heterogeneity.

scholarly journals Identification and Characterization of the Caspase-Mediated Apoptotic Activity of Teucrium mascatense and an Isolated Compound in Human Cancer Cells

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 977 ◽  
Author(s):  
Neena Panicker ◽  
Sameera Balhamar ◽  
Shaima Akhlaq ◽  
Mohammed Qureshi ◽  
Tania Rizvi ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Annexin V ◽  
Dependent Manner ◽  
Human Cancer Cells ◽  
Cell Death Pathways ◽  
Proliferative Effect ◽  
Mcf 7

Plants of the genus Teucrium (Lamiaceae or Labiatae family) are known historically for their medicinal value. Here, we identify and characterize the anticancer potential of T. mascatense and its active compound, IM60, in human cancer cells. The anti-proliferative effect of a T. mascatense methanol extract and its various fractions were analyzed in MCF-7 and HeLa cells in a dose- and time dependent manner. The dichloromethane fraction (TMDF) was observed to be the most effective with cytotoxicity against a more expanded series of cell lines, including MDA-MB-231. A time and dose-dependent toxicity profile was also observed for IM60; it could induce rapid cell death (within 3 h) in MCF-7 cells. Activation of caspases and PARP, hallmarks of apoptotic cell death pathways, following treatment with TMDF was demonstrated using western blot analysis. Inversion of the phosphatidylserine phospholipid from the inner to the outer membrane was confirmed by annexin V staining that was inhibited by the classical apoptosis inhibitor, Z-VAK-FMK. Changes in cell rounding, shrinkage, and detachment from other cells following treatment with TMDF and IM60 also supported these findings. Finally, the potential of TMDF and IM60 to induce enzymatic activity of caspases was also demonstrated in MCF-7 cells. This study, thus, not only characterizes the anticancer potential of T. mascatense, but also identifies a lead terpenoid, IM60, with the potential to activate anticancer cell death pathways in human cancer cells.

scholarly journals Design and Synthesis of Novel Dehydroepiandrosterone Analogues as Potent Antiproliferative Agents

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2243 ◽  
Author(s):  
Xing Huang ◽  
Qing-Kun Shen ◽  
Hong-Jian Zhang ◽  
Jia-Li Li ◽  
Yu-Shun Tian ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Line ◽  
Human Cancer ◽  
Cytotoxic Effects ◽  
Antiproliferative Effects ◽  
Human Cancer Cells ◽  
Design And Synthesis ◽  
Ic50 Value ◽  
G2 Phase ◽  
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The aim of the present study was to determine the cytotoxic effects of a series of novel dehydroepiandrosterone derivatives containing triazole at the C16 position on human cancer cells. The cancer cells used in the present study were A549, Hela, HepG-2, BEL7402, MCF-7, and HCT116. Several of the synthesised compounds exhibited potent antiproliferative effects. The most promising compound was (E)-3-hydroxy-16-((1-(4-iodophenyl)-1H-1,2,3-triazole-4-yl)methylene)-10,13-dimet-hyl-1,3,4,7,8,9,10,11,12,13,15,16-dodecahydro-2H-cyclopenta[a]phenanthren-17(14)-one (compound 2n), which showed considerably high antiproliferative activity in the HepG-2 cell line, with an IC50 value of 9.10 µM, and considerably high activity against the MCF-7 cell line, with an IC50 value of 9.18 µM. Flow cytometry assays demonstrated that compound 2n exerted antiproliferative effects by arresting cells in the G2 phase of the cell cycle and inducing apoptosis.

Cytotoxic effect of Berberis libanotica roots extracts on human cancer cells and antioxidant activities

2017 ◽  
Vol 6 (6) ◽  
pp. 311-317
Author(s):  
Kamar Hamade ◽  
◽  
Louna Karam ◽  
Jean Habib ◽  
Raghida Abou Merhi ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Cancer Cells ◽  
Cytotoxic Effect ◽  
Antioxidant Activities ◽  
Human Cancer ◽  
Medicinal Tree ◽  
Human Cancer Cells ◽  
Promising Source ◽  
Ht 29 ◽  
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In the present study, we evaluated the cytotoxic effect and the antioxidant activity of methanolic and ethanolic roots extracts obtained from Berberis libanotica a Lebanese medicinal tree. Cytotoxic activity was assessed on the colon cancer HT 29, HCT 116, Caco-2 and breast cancer MCF-7 and MDA-MB-231cell lines, using the MTT viability assay. Both extracts inhibited cancer cells proliferation in a doseand time depending manner without being cytotoxic against the normal MCF-10 cell line. Our results suggest that methanolic extract could induce a caspase-independent cell death in the colon and breast tumor cells HT 29 and MCF-7, respectively. DPPH and FRAP assays showed a moderate to strong antioxidant activity of the methanolic and ethanolic extracts with EC50 values of 0.13 ± 0.001 and 0.1± 0.002 mg/ml, respectively. Collectively, these findings suggest that Berberis libanotica roots could serve as a promising source of antioxidant and anticancer bioactive compounds.

Product of aromatase activity in intact LNCaP and MCF-7 human cancer cells

1997 ◽  
Vol 61 (3-6) ◽  
pp. 287-292 ◽  
Author(s):  
Luigi A.M. Castagnetta ◽  
Orazia M. Granata ◽  
Vincenzo Bellavia ◽  
Rosalba Amodio ◽  
Eugenia Scaccianoce ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Aromatase Activity ◽  
Human Cancer Cells ◽  
Mcf 7
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