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 ◽  
...  

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.

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1248
Author(s):  
Katarzyna Piszczatowska ◽  
Dorota Przybylska ◽  
Ewa Sikora ◽  
Grażyna Mosieniak

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.


Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 377
Author(s):  
Iván González-Chavarría ◽  
Felix Duprat ◽  
Francisco J. Roa ◽  
Nery Jara ◽  
Jorge R. Toledo ◽  
...  

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.


Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 977 ◽  
Author(s):  
Neena Panicker ◽  
Sameera Balhamar ◽  
Shaima Akhlaq ◽  
Mohammed Qureshi ◽  
Tania Rizvi ◽  
...  

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.


2012 ◽  
Vol 10 (32) ◽  
pp. 6537 ◽  
Author(s):  
Sebastian Müller ◽  
Deborah A. Sanders ◽  
Marco Di Antonio ◽  
Stephanos Matsis ◽  
Jean-François Riou ◽  
...  

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2243 ◽  
Author(s):  
Xing Huang ◽  
Qing-Kun Shen ◽  
Hong-Jian Zhang ◽  
Jia-Li Li ◽  
Yu-Shun Tian ◽  
...  

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.


2017 ◽  
Vol 6 (6) ◽  
pp. 311-317
Author(s):  
Kamar Hamade ◽  
◽  
Louna Karam ◽  
Jean Habib ◽  
Raghida Abou Merhi ◽  
...  

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.


1997 ◽  
Vol 61 (3-6) ◽  
pp. 287-292 ◽  
Author(s):  
Luigi A.M. Castagnetta ◽  
Orazia M. Granata ◽  
Vincenzo Bellavia ◽  
Rosalba Amodio ◽  
Eugenia Scaccianoce ◽  
...  

Pharmacia ◽  
2021 ◽  
Vol 68 (2) ◽  
pp. 353-363
Author(s):  
Hadeel M. Bayoumi ◽  
Mayson H. Alkhatib ◽  
Madeha N. Al-Seeni

Purpose: To investigate the modulatory effect of the natural phytochemical, carvacrol, on Topotecan (TOPO) cytotoxicity and cellular uptake in different cancer cell lines. Methods: The cytotoxicity of the carvacrol/TOPO combination therapy was determined in vitro using crystal violet assay. Coomassie blue and DAPI fluorescent stains were used for cellular morphology and molecular cell death assessments, respectively. Additionally, TOPO cellular uptake after carvacrol/TOPO combination therapy was determined. Results: Treatment of HeLa and HCT116 with carvacrol/TOPO resulted in 7.70- and 5.71-fold reduction in TOPO half maximal inhibitory concentration (IC50), respectively, relative to TOPO single treatment. On the other hand, treatment of MCF-7, HepG2, SKOV3, and A549 cancer cells with carvacrol/TOPO resulted in increasing the IC50 of TOPO by 1.49-, 1.33-, 1.50- and 1.26-fold, respectively, relative to TOPO single treatment. Conclusion: Carvacrol had enhanced TOPO cytotoxicity and cellular uptake in HeLa and HCT116 cancer cells but might cause TOPO resistance in MCF-7, HepG2, SKOV3 and A549 cells.


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