Abstract 2223: Membranous expression of programmed cell death-ligand 1 (PDL1) on cancer cells is induced by cisplatin in an ATR dependent manner

AbstractCompetitive cell-interactions play a crucial role in quality control during development and homeostasis. Here we show that cancer cells use such interactions to actively eliminate wild-type intestine cells in enteroid monolayers and organoids. This apoptosis-dependent process boosts proliferation of intestinal cancer cells. The remaining wild-type population activates markers of primitive epithelia and transits to a fetal-like state. Prevention of this cell fate transition avoids elimination of wild-type cells and, importantly, limits the proliferation of cancer cells. JNK signalling is activated in competing cells and is required for cell fate change and elimination of wild-type cells. Thus, cell competition drives growth of cancer cells by active out-competition of wild-type cells through forced cell death and cell fate change in a JNK dependent manner.

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Effect of Calomelanone, a Dihydrochalcone Analogue, on Human Cancer Apoptosis/Regulated Cell Death in an In Vitro Model

BioMed Research International ◽

10.1155/2020/4926821 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Wasitta Rachakhom ◽

Ratana Banjerdpongchai

Keyword(s):

Cell Death ◽

Cancer Cells ◽

Hepg2 Cells ◽

Cytotoxic Effect ◽

Human Cancer ◽

Autophagic Flux ◽

Dependent Manner ◽

Anticancer Activities ◽

Human Cancer Cells ◽

Regulated Cell Death

Calomelanone, 2 ′ ,6 ′ -dihydroxy-4,4 ′ -dimethoxydihydrochalcone, possesses anticancer activities. This study was conducted to investigate the cytotoxic effect of calomelanone, a dihydrochalcone analogue, on human cancer cells and its associated mechanisms. The cytotoxic effect of calomelanone was measured by MTT assay. Annexin V-FITC/propidium iodide and DiOC6 staining that employed flow cytometry were used to determine the mode of cell death and reduction of mitochondrial transmembrane potential (MTP), respectively. Caspase activities were measured using specific substrates and colorimetric analysis. The expression levels of Bcl-2 family proteins were determined by immunoblotting. Reactive oxygen species were also measured using 2 ′ ,7 ′ -dihydrodichlorofluorescein diacetate and dihydroethidium (fluorescence dyes). Calomelanone was found to be toxic towards various human cancer cells, including acute promyelocytic HL-60 and monocytic leukemic U937 cells, in a dose-dependent manner at 24 h and human hepatocellular HepG2 cells at 48 h. However, the proliferation of HepG2 cells increased at 24 h. Calomelanone was found to induce apoptosis in HL-60 and U937 at 24 h and HepG2 apoptosis at 48 h via the intrinsic pathway by inducing MTP disruption. This compound also induced caspase-3, caspase-8, and caspase-9 activities. Calomelanone upregulated proapoptotic Bax and Bak and downregulated antiapoptotic Bcl-xL proteins in HepG2 cells. Moreover, signaling was also associated with oxidative stress in HepG2 cells. Calomelanone induced autophagy at 24 h of treatment, which was evidenced by staining with monodansylcadaverine (MDC) to represent autophagic flux. This was associated with a decrease of Akt (survival pathway) and an upregulation of Atg5 (the marker of autophagy). Thus, calomelanone induced apoptosis/regulated cell death in HL-60, U937, and HepG2 cells. However, it also induced autophagy in HepG2 depending on duration, dose, and type of cells. Thus, calomelanone could be used as a potential anticancer agent for cancer treatment. Nevertheless, acute and chronic toxicity should be further investigated in animals before conducting investigations in human patients.

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BH3-only proteins are essential initiators of programmed cell death and stress-induced apoptosis in normal and cancer cells

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(08)71195-9 ◽

2008 ◽

Vol 6 (9) ◽

pp. 6

Author(s):

A. Strasser ◽

A. Villunger ◽

P. Bouillet ◽

E.M. Michalak ◽

L.A. O'Reilly ◽

...

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Cancer Cells ◽

Induced Apoptosis

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Methylglyoxal at metronomic doses sensitizes breast cancer cells to doxorubicin and cisplatin causing synergistic induction of programmed cell death and inhibition of stemness

Biochemical Pharmacology ◽

10.1016/j.bcp.2018.08.041 ◽

2018 ◽

Vol 156 ◽

pp. 322-339 ◽

Cited By ~ 8

Author(s):

Anirban Roy ◽

Sushmita Sarker ◽

Priyanka Upadhyay ◽

Aparajita Pal ◽

Arghya Adhikary ◽

...

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Programmed Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Synergistic Induction

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Regulation of programmed cell death by plasminogen activator inhibitor type 1 (PAI-1)

Thrombosis and Haemostasis ◽

10.1160/th08-04-0266 ◽

2008 ◽

Vol 100 (12) ◽

pp. 1041-1046 ◽

Cited By ~ 23

Author(s):

Maria Rømer ◽

Ulrik A. Lademann

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Cancer Cells ◽

Plasminogen Activator ◽

Cell Signalling ◽

Plasminogen Activator Inhibitor ◽

Plasminogen Activator Inhibitor 1 ◽

Activator Inhibitor Type ◽

Activator Inhibitor ◽

Pai 1

SummaryElevated levels of plasminogen activator inhibitor-1 (PAI-1) are associated with poor prognosis in cancer. An explanation to the elevated levels of PAI-1 could be a protective response to the increased proteolytic activity, caused by elevated levels of urokinase-type plasminogen activator (uPA) observed in tumours; however, several lines of evidence suggest that PAI-1 may contribute directly to the pathology of the disease. PAI-1 has been reported to have an effect on most of the basic cellular processes including cell adhesion, cell migration, cell invasion, and cell proliferation and increasing numbers of reports suggest that PAI-1 also can regulate programmed cell death (PCD) in cancer cells and normal cells.A number of reports suggest that PAI-1 can inhibit PCD through its pro-adhesive/anti-proteolytic property whereas other reports suggest that PAI-1 induces PCD through its anti-adhesive property.Furthermore,it has been suggested that PAI-1 can either induce or inhibit PCD though activation of cell signalling pathways.This review will focus on the regulation of programmed cell death by PAI-1 in both normal cells and cancer cells.

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Selective Suppression of Cell Growth and Programmed Cell Death-Ligand 1 Expression in HT1080 Fibrosarcoma Cells by Low Molecular Weight Fucoidan Extract

Marine Drugs ◽

10.3390/md17070421 ◽

2019 ◽

Vol 17 (7) ◽

pp. 421 ◽

Cited By ~ 3

Author(s):

Kiichiro Teruya ◽

Yoshihiro Kusumoto ◽

Hiroshi Eto ◽

Noboru Nakamichi ◽

Sanetaka Shirahata

Keyword(s):

Molecular Weight ◽

Cell Death ◽

Programmed Cell Death ◽

Cancer Cells ◽

Biological Activities ◽

Immune Surveillance ◽

Selective Inhibition ◽

Low Molecular Weight ◽

Fibrosarcoma Cells ◽

Self Protection

Low molecular weight fucoidan extract (LMF), prepared by an abalone glycosidase digestion of a crude fucoidan extracted from Cladosiphon novae-caledoniae Kylin, exhibits various biological activities, including anticancer effect. Various cancers express programmed cell death-ligand 1 (PD-L1), which is known to play a significant role in evasion of the host immune surveillance system. PD-L1 is also expressed in many types of normal cells for self-protection. Previous research has revealed that selective inhibition of PD-L1 expressed in cancer cells is critical for successful cancer eradication. In the present study, we analyzed whether LMF could regulate PD-L1 expression in HT1080 fibrosarcoma cells. Our results demonstrated that LMF suppressed PD-L1/PD-L2 expression and the growth of HT1080 cancer cells and had no effect on the growth of normal TIG-1 cells. Thus, LMF differentially regulates PD-L1 expression in normal and cancer cells and could serve as an alternative complementary agent for treatment of cancers with high PD-L1 expression.

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Neferine induces autophagy-dependent cell death in apoptosis-resistant cancers via ryanodine receptor and Ca2+-dependent mechanism

Scientific Reports ◽

10.1038/s41598-019-56675-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 7

Author(s):

Betty Yuen Kwan Law ◽

Francesco Michelangeli ◽

Yuan Qing Qu ◽

Su-Wei Xu ◽

Yu Han ◽

...

Keyword(s):

Cell Death ◽

Cancer Therapy ◽

Cancer Cells ◽

Ryanodine Receptor ◽

Calcium Release ◽

Receptor Activation ◽

Autophagic Cell Death ◽

Dependent Manner ◽

Computational Docking ◽

Calcium Dependent

AbstractResistance of cancer cells to chemotherapy is a significant clinical concern and mechanisms regulating cell death in cancer therapy, including apoptosis, autophagy or necrosis, have been extensively investigated over the last decade. Accordingly, the identification of medicinal compounds against chemoresistant cancer cells via new mechanism of action is highly desired. Autophagy is important in inducing cell death or survival in cancer therapy. Recently, novel autophagy activators isolated from natural products were shown to induce autophagic cell death in apoptosis-resistant cancer cells in a calcium-dependent manner. Therefore, enhancement of autophagy may serve as additional therapeutic strategy against these resistant cancers. By computational docking analysis, biochemical assays, and advanced live-cell imaging, we identified that neferine, a natural alkaloid from Nelumbo nucifera, induces autophagy by activating the ryanodine receptor and calcium release. With well-known apoptotic agents, such as staurosporine, taxol, doxorubicin, cisplatin and etoposide, utilized as controls, neferine was shown to induce autophagic cell death in a panel of cancer cells, including apoptosis-defective and -resistant cancer cells or isogenic cancer cells, via calcium mobilization through the activation of ryanodine receptor and Ulk-1-PERK and AMPK-mTOR signaling cascades. Taken together, this study provides insights into the cytotoxic mechanism of neferine-induced autophagy through ryanodine receptor activation in resistant cancers.

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