scholarly journals Chemopreventive Effect of β-Cryptoxanthin on Human Cervical Carcinoma (HeLa) Cells Is Modulated through Oxidative Stress-Induced Apoptosis

Antioxidants ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 28 ◽  
Author(s):  
Enkhtaivan Gansukh ◽  
Arti Nile ◽  
Iyyakkannu Sivanesan ◽  
Kannan R. R. Rengasamy ◽  
Doo-Hwan Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cervical Carcinoma ◽  
Hela Cells ◽  
Caspase 3 ◽  
Nuclear Condensation ◽  
Physiological Concentration ◽  
Human Cervical Carcinoma ◽  
Induced Apoptosis

The present study was aimed to assess cellular and molecular events involved in the chemopreventive activities of β-cryptoxanthin derived from mandarin oranges (Citrus unshiu Marc.) on human cervical carcinoma (HeLa) cells. In vitro experiments established that β-cryptoxanthin significantly inhibited the proliferation of HeLa cells with the IC50 value of 4.5 and 3.7 µM after 24 and 48 h of treatments, respectively. β-cryptoxanthin-treated HeLa cells exhibited enhanced levels of oxidative stress correlated with significant downregulation of anti-apoptotic Bcl-2, and upregulation of pro-apoptotic Bax mRNA expression. Moreover, β-cryptoxanthin triggered nuclear condensation and disruption of the integrity of the mitochondrial membrane, upregulated caspase-3, -7, and -9 mRNA, and enhanced activation of caspase-3 proteins, resulting in nuclei DNA damage and apoptosis of HeLa cells. Remarkably, TUNEL assay carried out to detect nuclei DNA damage showed 52% TUNEL-positive cells after treatment with a physiological concentration of β-cryptoxanthin (1.0 μM), which validates its potential as an anticancer drug of natural origin.

Wogonin induces G1 phase arrest through inhibiting Cdk4 and cyclin D1 concomitant with an elevation in p21Cip1 in human cervical carcinoma HeLa cells

2009 ◽  
Vol 87 (6) ◽  
pp. 933-942 ◽  
Author(s):  
Li Yang ◽  
Hai-wei Zhang ◽  
Rong Hu ◽  
Yong Yang ◽  
Qi Qi ◽  
...  
Keyword(s):  
Cyclin D1 ◽  
Cervical Carcinoma ◽  
Hela Cells ◽  
Therapeutic Potential ◽  
P53 Gene ◽  
Mrna Levels ◽  
Human Cervical Carcinoma ◽  
Phase Arrest

Wogonin, a naturally occurring flavonoid, has been shown to have tumor therapeutic potential both in vitro and in vivo. To better understand its anticancer mechanism, we examined the effect of wogonin on human cervical carcinoma HeLa cells. In this study, we observed that G1 phase arrest was involved in wogonin-induced growth inhibition in HeLa cells. Over a 24 h exposure of HeLa cells to 90 µmol·L–1 wogonin, the promoters of G1–S transition, including cyclin D1/Cdk4 and pRb, decreased within 12 h and E2F-1 depleted in the nucleus at the same time. As the G1 phase arrest developed, p53 and the Cdk inhibitor p21Cip1 elevated both at protein and mRNA levels. Furthermore, the up-regulation of p21Cip1 induced by wogonin was dramatically inhibited by siRNA-mediated p53 gene silencing. Collectively, our data suggested that wogonin induced G1 phase arrest in HeLa cells by modulating several key G1 regulatory proteins, such as Cdk4 and cyclin D1, as well as up-regulation of a p53-midiated p21Cip1 expression. This mechanism of wogonin may play an important role in the killing of cancerous cells and offer a potential mechanism for its anticancer action in vivo.

scholarly journals NF-κB, Caspase-3 and p53 Pathways are Involved in Resveratrol-Chitosan Nanoparticles-Induced Apoptosis in Hela Cells with Oxidative Stress

2021 ◽  
Vol 5 (5) ◽  
pp. 128-137
Author(s):  
Mohammed A Hussein ◽  
Raghad M Mahmmed ◽  
Afnan A Sebawaih ◽  
Basma A El-Maghraby ◽  
Eman E Mohammed ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hela Cells ◽  
Caspase 3 ◽  
Chitosan Nanoparticles ◽  
Induced Apoptosis

scholarly journals Identification of Spiro-Fused Pyrrolo[3,4-a]pyrrolizines and Tryptanthrines as Potential Antitumor Agents: Synthesis and In Vitro Evaluation

2021 ◽  
Vol 22 (21) ◽  
pp. 11997
Author(s):  
Diana. K. Latypova ◽  
Stanislav V. Shmakov ◽  
Sofya A. Pechkovskaya ◽  
Alexander S. Filatov ◽  
Alexander V. Stepakov ◽  
...  
Keyword(s):  
Hela Cell ◽  
Cell Line ◽  
Cervical Carcinoma ◽  
Hela Cells ◽  
Antitumor Agents ◽  
Hela Cell Lines ◽  
M Phase ◽  
Induced Apoptosis ◽  
Potential Antitumor

A series of heterocyclic compounds containing a spiro-fused pyrrolo[3,4-a]pyrrolizine and tryptanthrin framework have been synthesized and studied as potential antitumor agents. Cytotoxicity of products was screened against human erythroleukemia (K562) and human cervical carcinoma (HeLa) cell lines. Among the screened compounds. 4a, 4b and 5a were active against human erythroleukemia (K562) cell line, while 4a and 5a were active against cervical carcinoma (HeLa) cell line. In agreement with the DNA cytometry studies, the tested compounds have achieved significant cell-cycle perturbation with higher accumulation of cells in G2/M phase and induced apoptosis. Using confocal microscopy, we found that with 4a and 5a treatment of HeLa cells, actin filaments disappeared, and granular actin was distributed diffusely in the cytoplasm in 76–91% of cells. We discovered that HeLa cells after treatment with compounds 4a and 5a significantly reduced the number of cells with filopodium-like membrane protrusions (from 63 % in control cells to 29% after treatment) and a decrease in cell motility.

Abstract TP265: AATF Protects Neuron Against Ischemia via Regulating PAR/AIF Pathway

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Wei Jin ◽  
Wei Xu ◽  
Jing Chen ◽  
Xiaoxiao Zhang ◽  
Chuancheng Ren
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Western Blot ◽  
Dna Fragmentation ◽  
Caspase 3 ◽  
Immunofluorescent Staining ◽  
Dependent Manner ◽  
Cellular Death ◽  
Cell Death Pathway

Abstract: Apoptosis antagonizing transcription factor (AATF) exerts an effect against oxidative stress, DNA damage and cellular apoptosis. However, its role in neuronal ischemia or hypoxia damage has not been elucidated yet. Present study investigated the neuroprotective roles and mechanisms of AATF under ischemia and hypoxia in vivo and in vitro. Focal cerebral ischemia of rat was generated by distal middle cerebral artery occlusion (dMCAO) model, SH-SY5Y cells were used to generate oxygen glucose deprivation (OGD) model in vitro. Western blot and immunofluorescent staining were used to investigate the expression changes of AATF. CCK-8 and LDH were performed to evaluate cellular survival and cytotoxicity. Overexpression and interference lentivirus vectors were performed to regulate the expression of AATF in SH-SY5Y cells. DHE staining that measured by flow cytometry was performed to investigate cellular superoxide anion levels. 8-OHdG expression and AP sites measurement were used to evaluate DNA damage. DNA Ladder and TUNEL staining were employed to evaluate DNA fragmentation. MNNG and DPQ were respectively used to agitate or antagonist caspase-3 independent PCD (programmed cell death) pathway, STS and Z-VAD-fmk were respectively used to agitate or antagonist caspase-3 dependent PCD pathway. Western blot was performed to investigate the expression of Poly(ADP-ribose) polymers (PAR) and apoptosis inducing factor (AIF) in different cellular components, Co-IP (co-immunoprecipitation) was used to test the interaction of AIF, H2AX and CypA (Cyclophilin A). We found that AATF was increased in cortical neurons after brain ischemia (P<0.001). Besides, AATF was upregulated in OGD-treated SH-SY5Y cells in a time-dependent manner (P=0.007). Additionally, overexpressing AATF ameliorated OGD-induced cellular death (P < 0.001) and cytotoxicity (P = 0.001), and AATF interference exacerbated OGD-induced cellular death (P=0.033) and cytotoxicity (P=0.006). We also found that AATF overexpression suppressed cellular DNA fragmentation (P=0.003) but did not ameliorate oxidative stress and DNA damage. Moreover, we discovered that overexpressing AATF suppressed PAR/AIF signaling pathway via binding with AIF.

Yuk-Hap-Tang Induces Apoptosis by Intervening Mn-SOD in Human Cervical Carcinoma HeLa Cells

2004 ◽  
Vol 32 (06) ◽  
pp. 883-895 ◽  
Author(s):  
H. J. Chae ◽  
J. M. Park ◽  
G. Y. Lee ◽  
H. R. Park ◽  
S. W. Chae ◽  
...  
Keyword(s):  
Cell Death ◽  
Cervical Carcinoma ◽  
Anticancer Agents ◽  
Hela Cells ◽  
Caspase 3 ◽  
Reduced Glutathione ◽  
Cleavage Product ◽  
P53 Expression ◽  
Human Cervical Carcinoma ◽  
Apoptotic Protein

Yuk-Hap-Tang (YHT) induces cell death in human cervical carcinoma HeLa cells. Caspase-3, -6 and -9 were markedly activated in HeLa cells treated with YHT. The preferred substrate for caspase-3 cysteine protease, PARP, was cleaved to its 85-kDa cleavage product. YHT increased the amount of the anti-apoptotic protein, Bcl-2, and the pro-apoptotic protein, Bax. Although p53 has been reported to accumulate in cancer cells in response to anticancer agents, the p53 expression level was not changed in HeLa cells treated with YHT. Manganese (Mn)-TBAP, a mitochondria-specific SOD mimetic agent and NAC/GSH (N-acetyl cysteine/reduced glutathione) reduced the YHT-induced cytotoxicity and decreased the number of the YHT-induced apoptotic cells. Furthermore, YHT reduced the expression of Mn-SOD protein and its activity in HeLa cells. The data demonstrate that YHT induces the apoptosis of human cervical carcinoma HeLa cells by intervening Mn-SOD.

scholarly journals Role for Caspase-Mediated Cleavage of Rad51 in Induction of Apoptosis by DNA Damage

1999 ◽  
Vol 19 (4) ◽  
pp. 2986-2997 ◽  
Author(s):  
YinYin Huang ◽  
Shuji Nakada ◽  
Takatoshi Ishiko ◽  
Taiju Utsugisawa ◽  
Rakesh Datta ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Mammalian Cells ◽  
Caspase 3 ◽  
Apoptotic Response ◽  
Cell Death Response ◽  
Induction Of Apoptosis ◽  
Induced Apoptosis ◽  
Dependent Mechanism

ABSTRACT We report here that the Rad51 recombinase is cleaved in mammalian cells during the induction of apoptosis by ionizing radiation (IR) exposure. The results demonstrate that IR induces Rad51 cleavage by a caspase-dependent mechanism. Further support for involvement of caspases is provided by the finding that IR-induced proteolysis of Rad51 is inhibited by Ac-DEVD-CHO. In vitro studies show that Rad51 is cleaved by caspase 3 at a DVLD/N site. Stable expression of a Rad51 mutant in which the aspartic acid residues were mutated to alanines (AVLA/N) confirmed that the DVLD/N site is responsible for the cleavage of Rad51 in IR-induced apoptosis. The functional significance of Rad51 proteolysis is supported by the finding that, unlike intact Rad51, the N- and C-terminal cleavage products fail to exhibit recombinase activity. In cells, overexpression of the Rad51(D-A) mutant had no effect on activation of caspase 3 but did abrogate in part the apoptotic response to IR exposure. We conclude that proteolytic inactivation of Rad51 by a caspase-mediated mechanism contributes to the cell death response induced by DNA damage.

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