The roles of mitochondria in radiation-induced autophagic cell death in 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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SERPINB3 (SCCA1) inhibits cathepsin L and lysoptosis, protecting cervical cancer cells from chemoradiation

Communications Biology ◽

10.1038/s42003-021-02893-6 ◽

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.

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Two species of Ulva inhibits the progression of cervical cancer cells SiHa by means of autophagic cell death induction

3 Biotech ◽

10.1007/s13205-020-02576-9 ◽

2021 ◽

Vol 11 (2) ◽

Author(s):

Asmita Pal ◽

Preeti Verma ◽

Subhabrata Paul ◽

Indira Majumder ◽

Rita Kundu

Keyword(s):

Cervical Cancer ◽

Cell Death ◽

Cancer Cells ◽

Autophagic Cell Death ◽

Cervical Cancer Cells

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Retraction: Down-regulation of the radiation-induced pEGFRThr654 mediated activation of DNA-PK by Cetuximab in cervical cancer cells

RSC Advances ◽

10.1039/d1ra90037d ◽

2021 ◽

Vol 11 (9) ◽

pp. 5021-5021

Author(s):

Laura Fisher

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Down Regulation ◽

Cervical Cancer Cells ◽

Radiation Induced

Retraction of ‘Down-regulation of the radiation-induced pEGFRThr654 mediated activation of DNA-PK by Cetuximab in cervical cancer cells’ by Yunxiang Qi et al., RSC Adv., 2020, 10, 1132–1141, DOI: 10.1039/C9RA04962B.

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The role of p38 MAPK and JNK in Arsenic trioxide-induced mitochondrial cell death in human cervical cancer cells

Journal of Cellular Physiology ◽

10.1002/jcp.21470 ◽

2008 ◽

Vol 217 (1) ◽

pp. 23-33 ◽

Cited By ~ 70

Author(s):

Young-Hee Kang ◽

Su-Jae Lee

Keyword(s):

Cervical Cancer ◽

Cell Death ◽

Cancer Cells ◽

Arsenic Trioxide ◽

P38 Mapk ◽

Cervical Cancer Cells ◽

Human Cervical Cancer Cells ◽

Human Cervical Cancer

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Chloroform fraction of Chaetomorpha brachygona, a marine green alga from Indian Sundarbans inducing autophagy in cervical cancer cells in vitro

Scientific Reports ◽

10.1038/s41598-020-78592-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Indira Majumder ◽

Subhabrata Paul ◽

Anish Nag ◽

Rita Kundu

Keyword(s):

Cervical Cancer ◽

Cell Death ◽

Cancer Cells ◽

Green Alga ◽

Chloroform Fraction ◽

Anticancer Activities ◽

Siha Cell Line ◽

Cervical Cancer Cells ◽

Marine Green Alga

AbstractSundarbans Mangrove Ecosystem (SME) is a rich repository of bioactive natural compounds, with immense nutraceutical and therapeutic potential. Till date, the algal population of SME was not explored fully for their anticancer activities. Our aim is to explore the potential of these algal phytochemicals against the proliferation of cervical cancer cells (in vitro) and identify the mode of cell death induced in them. In the present work, the chloroform fraction of marine green alga, Chaetomorpha brachygona was used on SiHa cell line. The algal phytochemicals were identified by GCMS, LCMS and column chromatography and some of the identified compounds, known for significant anticancer activities, have shown strong Bcl-2 binding capacity, as analyzed through molecular docking study. The extract showed cytostatic and cytotoxic activity on SiHa cells. Absence of fragmented DNA, and presence of increased number of acidic vacuoles in the treated cells indicate nonapoptotic cell death. The mode of cell death was likely to be autophagic, as indicated by the enhanced expression of Beclin 1 and LC3BII (considered as autophagic markers) observed by Western blotting. The study indicates that, C. brachygona can successfully inhibit the proliferation of cervical cancer cells in vitro.

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