scholarly journals Up-regulation of FLIP in cisplatin-selected HeLa cells causes cross-resistance to CD95/Fas death signalling

2003 ◽  
Vol 376 (1) ◽  
pp. 253-260 ◽  
Author(s):  
Pachiyappan KAMARAJAN ◽  
Nian-Kang SUN ◽  
Chuck C.-K. CHAO
Keyword(s):  
Cell Surface ◽  
Hela Cell ◽  
Cell Lines ◽  
Antisense Oligonucleotides ◽  
Cross Resistance ◽  
Caspase 8 ◽  
Cervix Carcinoma ◽  
Hela Cell Lines ◽  
Induced Apoptosis ◽  
Resistant Cells

Cisplatin-selected cervix carcinoma HeLa cell lines induced less apoptosis, and weaker activation by cisplatin or Fas-activating antibody, of mitochondrial-associated caspase-9 and death receptor-mediated caspase-8 than did parental cells. Furthermore, less DISC (death-inducing signalling complex) was formed in cisplatin-selected cell lines than in parental cells. Ac-IETD-CHO (acetyl-Ile-Glu-Thr-Asp-aldehyde), which has a certain preference for inhibiting caspase-8, or Fas-antagonistic antibody, significantly inhibited cisplatin-induced apoptosis in both parental and cisplatin-selected HeLa cell lines. These results imply that cell-surface death signalling is inducible by cisplatin; that reduction of this pathway is associated with drug resistance, and that cisplatin-selected cells acquire cross-resistance to cell-surface death signalling. Sequential up-regulation of FLIP (FLICE-like inhibitory protein), but not Bcl-2, Bcl-xL or inhibitors of apoptosis protein (IAPs), was observed in resistant cells but not in parental cells. The inhibition of FLIP by FLIP antisense oligonucleotides promotes cisplatin and Fas-antibody-induced apoptosis. However, the modulation of apoptosis by FLIP antisense oligonucleotides in resistant cells is greater than that in parental cells. The presented data reveal that the up-regulation of FLIP may contribute to the suppression of apoptosis and thereby change cells that are resistant to cisplatin and Fas-mediated death signals. The results also show that cancer cells that have undergone long-term chemotherapy and become chemoresistant may change the FLIP level, becoming cross-resistant to death factors such as Fas.

scholarly journals Modulation of RhoA GTPase Activity Sensitizes Human Cervix Carcinoma Cells toγ-Radiation by Attenuating DNA Repair Pathways

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Juliana H. Osaki ◽  
Gisele Espinha ◽  
Yuli T. Magalhaes ◽  
Fabio L. Forti
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Hela Cell ◽  
Cell Lines ◽  
Dominant Negative ◽  
Cervix Carcinoma ◽  
Gtpase Activity ◽  
Rhoa Activity ◽  
Rhoa Gtpase ◽  
Hela Cell Lines

Radiotherapy withγ-radiation is widely used in cancer treatment to induce DNA damage reducing cell proliferation and to kill tumor cells. Although RhoA GTPase overexpression/hyperactivation is observed in many malignancies, the effect of RhoA activity modulation on cancer radiosensitivity has not been previously investigated. Here, we generated stable HeLa cell clones expressing either the dominant negative RhoA-N19 or the constitutively active RhoA-V14 and compared the responses of these cell lines with those of parental HeLa cells, after treatment with low doses ofγ-radiation. HeLa-RhoA-N19 and HeLa-RhoA-V14 clones displayed reduced proliferation and survival compared to parental cells after radiation and became arrested at cell cycle stages correlated with increased cellular senescence and apoptosis. Also, Chk1/Chk2 and histone H2A phosphorylation data, as well as comet assays, suggest that the levels of DNA damage and DNA repair activation and efficiency in HeLa cell lines are correlated with active RhoA. In agreement with these results, RhoA inhibition by C3 toxin expression drastically affected homologous recombination (HR) and nonhomologous end joining (NHEJ). These data suggest that modulation of RhoA GTPase activity impairs DNA damage repair, increasing HeLa cell radiosensitivity.

Effect of black seeds (Nigella sativa) volatile oil on the cervical cancer: In vitro study, on Hela cell lines

2019 ◽  
Vol 7 (4) ◽  
pp. 91-96
Author(s):  
Isra'a Al-sobhi ◽  
◽  
Rawan Al-Ghabban ◽  
Soad Shaker Ali ◽  
Jehan Al-Amri ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Hela Cell ◽  
Cell Lines ◽  
Nigella Sativa ◽  
In Vitro Study ◽  
Volatile Oil ◽  
Vitro Study ◽  
Hela Cell Lines ◽  
Black Seeds

scholarly journals Structures, Chemical Conversions, and Cytotoxicity of Tricholopardins C and D, Two Tricholoma Triterpenoids from the Wild Mushroom Tricholoma pardinum

2021 ◽  
Author(s):  
Chen Shi ◽  
Yue-Ling Peng ◽  
Juan He ◽  
Zheng-Hui Li ◽  
Ji-Kai Liu ◽  
...  
Keyword(s):  
Hela Cell ◽  
Single Crystal ◽  
Cell Lines ◽  
Cell Apoptosis ◽  
Spectroscopic Methods ◽  
Wild Mushroom ◽  
X Ray Diffraction ◽  
X Ray ◽  
Hela Cell Lines ◽  
Mcf 7

AbstractTwo undescribed Tricholoma triterpenoids, namely tricholopardins C (1) and D (2), were isolated from the wild mushroom Tricholoma pardinum. Their structures with absolute configurations were elucidated by spectroscopic methods, as well as the single crystal X-ray diffraction. Compounds 1 and 2 were further obtained by chemical conversions from the known analogues. Compound 1 showed significant cytotoxicity to MCF-7 and Hela cell lines with IC50 values of 4.7 μM and 9.7 μM, respectively. Its mechanism of inducing MCF-7 cell apoptosis was studied briefly. Graphical Abstract

Cytotoxic effects of C-glycosides in HOS and HeLa cell lines

2007 ◽  
Vol 17 (13) ◽  
pp. 3676-3681 ◽  
Author(s):  
Carlos A. Sanhueza ◽  
Carlos Mayato ◽  
Rubén P. Machı´n ◽  
José M. Padrón ◽  
Rosa L. Dorta ◽  
...  
Keyword(s):  
Hela Cell ◽  
Cell Lines ◽  
Cytotoxic Effects ◽  
Hela Cell Lines

Caspase-2 is activated at the CD95 death-inducing signaling complex in the course of CD95-induced apoptosis

Blood ◽  
2006 ◽  
Vol 108 (2) ◽  
pp. 559-565 ◽  
Author(s):  
Inna N. Lavrik ◽  
Alexander Golks ◽  
Simone Baumann ◽  
Peter H. Krammer
Keyword(s):  
B Cell ◽  
Molecular Mechanism ◽  
Cell Lines ◽  
Caspase 8 ◽  
Signaling Complex ◽  
Deficient Cell ◽  
Apoptotic Pathways ◽  
Caspase 2 ◽  
Induced Apoptosis

Caspase-2 was reported to be involved in a number of apoptotic pathways triggered by various stimuli. However, the molecular mechanism of procaspase-2 activation in the course of apoptosis remains poorly defined. In this report, we demonstrate that procaspase-2 is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex (DISC) in human T- and B-cell lines. We show that procaspase-2 is activated at the DISC on CD95 stimulation. Despite its presence at the DISC, caspase-2 does not initiate apoptosis on CD95 stimulation in caspase-8–deficient cell lines. Taken together, our data reveal that caspase-2 is activated at the DISC but does not play an initiating role in the CD95-induced apoptosis.

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