scholarly journals Cathepsin L mediates resveratrol-induced autophagy and apoptotic cell death in cervical cancer cells

Autophagy ◽  
2009 ◽  
Vol 5 (4) ◽  
pp. 451-460 ◽  
Author(s):  
Keng-Fu Hsu ◽  
Chao-Liang Wu ◽  
Soon-Cen Huang ◽  
Ching-Ming Wu ◽  
Jenn-Ren Hsiao ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Cathepsin L ◽  
Apoptotic Cell Death ◽  
Cervical Cancer Cells

scholarly journals Lignan enriched fraction (LRF) of Phyllanthus amarus promotes apoptotic cell death in human cervical cancer cells in vitro

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Subhabrata Paul ◽  
Debashis Patra ◽  
Rita Kundu
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Growth Substance ◽  
Apoptotic Cell Death ◽  
Chloroform Fraction ◽  
Phyllanthus Amarus ◽  
Cervical Cancer Cells

Abstract Phyllanthus amarus is widely grown in this sub-continent and used traditionally to treat many common ailments. In the present study, lignan rich fraction of P. amarus extract was used on cervical cancer cell lines (HeLa, SiHa and C33A) to study it’s mechanism of cell death induction. As the cells were treated with IC50 doses of LRF, characteristic apoptotic features were observed. Increased sub G0 population were observed both in Hela and C33 cells, while G1/S arrest was observed in SiHa cells than their untreated counterparts. Increased production of ROS and change in MMP were also detected in the treated cells. Presence of γH2AX, was observed by immunofluorescence. Reduced expression of HPV (16/18) as well as ET-1, an autocrine growth substance, were observed in the treated cells. Immunoblotting as well as ICFC studies showed enhanced expressions of BAX, Caspase 3 and PARP (cleaved) in the treated cells. A major lignan, phyllanthin was isolated from the chloroform fraction and showed strong irreversible affinities for viral E6 and MDM2 in in silico analysis. The study conclusively indicates that LRF has the potential to induce apoptotic cell death in cervical cancer cells by activation of p53 and p21 against DNA damage.

scholarly journals Butein induces apoptotic cell death of human cervical cancer cells

2018 ◽  
Author(s):  
Pei‑Yu Yang ◽  
Dan‑Ning Hu ◽  
Ying‑Hsien Kao ◽  
I‑Ching Lin ◽  
Fu‑Shing Liu
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Cervical Cancer Cells ◽  
Human Cervical Cancer Cells ◽  
Human Cervical Cancer

scholarly journals Parkin induces apoptotic cell death in TNF-α-treated cervical cancer cells

BMB Reports ◽  
2012 ◽  
Vol 45 (9) ◽  
pp. 526-531 ◽  
Author(s):  
Kyung-Hong Lee ◽  
Min-Ho Lee ◽  
Yeo-Wool Kang ◽  
Ki-Jong Rhee ◽  
Tae-Ue Kim ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Tnf Α ◽  
Cervical Cancer Cells

scholarly journals Quinacrine-Induced Autophagy in Ovarian Cancer Triggers Cathepsin-L Mediated Lysosomal/Mitochondrial Membrane Permeabilization and Cell Death

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2004
Author(s):  
Prabhu Thirusangu ◽  
Christopher L. Pathoulas ◽  
Upasana Ray ◽  
Yinan Xiao ◽  
Julie Staub ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cytochrome C ◽  
Cancer Cells ◽  
Apoptotic Cell ◽  
Cathepsin L ◽  
Membrane Permeabilization ◽  
Apoptotic Cell Death ◽  
Ovarian Cancer Cells ◽  
Autophagic Flux

We previously reported that the antimalarial compound quinacrine (QC) induces autophagy in ovarian cancer cells. In the current study, we uncovered that QC significantly upregulates cathepsin L (CTSL) but not cathepsin B and D levels, implicating the specific role of CTSL in promoting QC-induced autophagic flux and apoptotic cell death in OC cells. Using a Magic Red® cathepsin L activity assay and LysoTracker red, we discerned that QC-induced CTSL activation promotes lysosomal membrane permeability (LMP) resulting in the release of active CTSL into the cytosol to promote apoptotic cell death. We found that QC-induced LMP and CTSL activation promotes Bid cleavage, mitochondrial outer membrane permeabilization (MOMP), and mitochondrial cytochrome-c release. Genetic (shRNA) and pharmacological (Z-FY(tBU)-DMK) inhibition of CTSL markedly reduces QC-induced autophagy, LMP, MOMP, apoptosis, and cell death; whereas induced overexpression of CTSL in ovarian cancer cell lines has an opposite effect. Using recombinant CTSL, we identified p62/SQSTM1 as a novel substrate of CTSL, suggesting that CTSL promotes QC-induced autophagic flux. CTSL activation is specific to QC-induced autophagy since no CTSL activation is seen in ATG5 knockout cells or with the anti-malarial autophagy-inhibiting drug chloroquine. Importantly, we showed that upregulation of CTSL in QC-treated HeyA8MDR xenografts corresponds with attenuation of p62, upregulation of LC3BII, cytochrome-c, tBid, cleaved PARP, and caspase3. Taken together, the data suggest that QC-induced autophagy and CTSL upregulation promote a positive feedback loop leading to excessive autophagic flux, LMP, and MOMP to promote QC-induced cell death in ovarian cancer cells.

scholarly journals SERPINB3 (SCCA1) inhibits cathepsin L and lysoptosis, protecting cervical cancer cells from chemoradiation

2022 ◽  
Vol 5 (1) ◽  
Author(s):  
Songyan Wang ◽  
Cliff J. Luke ◽  
Stephen C. Pak ◽  
Victoria Shi ◽  
Liyun Chen ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Death ◽  
Protease Inhibitor ◽  
Cancer Cells ◽  
Cathepsin L ◽  
Cysteine Protease Inhibitor ◽  
Knock Out ◽  
Lysosomal Protease ◽  
Cervical Cancer Cells ◽  
Radiation Induced

AbstractThe endogenous lysosomal cysteine protease inhibitor SERPINB3 (squamous cell carcinoma antigen 1, SCCA1) is elevated in patients with cervical cancer and other malignancies. High serum SERPINB3 is prognostic for recurrence and death following chemoradiation therapy. Cervical cancer cells genetically lacking SERPINB3 are more sensitive to ionizing radiation (IR), suggesting this protease inhibitor plays a role in therapeutic response. Here we demonstrate that SERPINB3-deficient cells have enhanced sensitivity to IR-induced cell death. Knock out of SERPINB3 sensitizes cells to a greater extent than cisplatin, the current standard of care. IR in SERPINB3 deficient cervical carcinoma cells induces predominantly necrotic cell death, with biochemical and cellular features of lysoptosis. Rescue with wild-type SERPINB3 or a reactive site loop mutant indicates that protease inhibitory activity is required to protect cervical tumor cells from radiation-induced death. Transcriptomics analysis of primary cervix tumor samples and genetic knock out demonstrates a role for the lysosomal protease cathepsin L in radiation-induced cell death in SERPINB3 knock-out cells. These data support targeting of SERPINB3 and lysoptosis to treat radioresistant cervical cancers.

scholarly journals Plumbagin triggers redox-mediated autophagy through the LC3B protein in human papillomavirus-positive cervical cancer cells

2020 ◽  
Author(s):  
Vaiyapuri Subbarayan Periasamy ◽  
Jegan Athinarayanan ◽  
Girija Ramankutty ◽  
Mohammad A. Akbarsha ◽  
Ali A. Alshatwi
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Flow Cytometry ◽  
Cell Death ◽  
Human Papillomavirus ◽  
Cancer Cells ◽  
Strong Evidence ◽  
Apoptotic Cell ◽  
Autophagic Cell Death ◽  
Cervical Cancer Cells

IntroductionIn this study, we analyzed the effect of plumbagin (PL) on cultured SiHa cervical cancer cells using fluorescence microscopy and flow cytometry techniques to identify the mode of cell death and to elucidate whether cells die through apoptosis or non-apoptosis.Material and methodsThe cell death was analyzed using MTT assay. The cellular morphological changes were assessed using acridine orange/ethidium bromide dual staining. DNA damage and cell cycle progression were analyzed using a comet assay and flow cytometry respectively.ResultsMorphological and cytological features revealed that PL induced autophagic cell death in cancer cells. The results of a cell cycle analysis indicated that the proportion of cells in sub-G0 phase increased. Translocation of LC-3B protein from the cytoplasm to the autophagosome was found in 31% of PL-treated cells, suggesting that PL provoked autophagic cell death. In this study, it was observed that plumbagin treatment caused cleavage of DNA in SiHa cancer cells, and morphological analysis provided very strong evidence supporting the occurrence of autophagic cell death as a result of plumbagin treatment.ConclusionsIn addition, a Cytoscape-based protein-PL interaction network analysis provided very strong evidence in support of the specific mode of cell death in the context of autophagy, which has also been one of the desired endpoints in human papillomavirus-positive cervical cancer therapy and apoptotic cell death-resistant cancer treatment. Thus, this study is the first to test PL against the SiHa cervical cancer cell line, providing leads for further testing on non-apoptotic cell death for application in cervical cancer management.

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