Tumor cytotoxicity and immunogenicity of a novel V-jet neon plasma source compared to the kINPen

AbstractRecent research indicated the potential of cold physical plasma in cancer therapy. The plethora of plasma-derived reactive oxygen and nitrogen species (ROS/RNS) mediate diverse antitumor effects after eliciting oxidative stress in cancer cells. We aimed at exploiting this principle using a newly designed dual-jet neon plasma source (Vjet) to treat colorectal cancer cells. A treatment time-dependent ROS/RNS generation induced oxidation, growth retardation, and cell death within 3D tumor spheroids were found. In TUM-CAM, a semi in vivo model, the Vjet markedly reduced vascularized tumors' growth, but an increase of tumor cell immunogenicity or uptake by dendritic cells was not observed. By comparison, the argon-driven single jet kINPen, known to mediate anticancer effects in vitro, in vivo, and in patients, generated less ROS/RNS and terminal cell death in spheroids. In the TUM-CAM model, however, the kINPen was equivalently effective and induced a stronger expression of immunogenic cancer cell death (ICD) markers, leading to increased phagocytosis of kINPen but not Vjet plasma-treated tumor cells by dendritic cells. Moreover, the Vjet was characterized according to the requirements of the DIN-SPEC 91315. Our results highlight the plasma device-specific action on cancer cells for evaluating optimal discharges for plasma cancer treatment.

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In vitro evaluation of estrogenic, antiestrogenic and antitumor effects of amentoflavone

Human & Experimental Toxicology ◽

10.1177/0960327121999454 ◽

2021 ◽

pp. 096032712199945

Author(s):

AT Aliyev ◽

S Ozcan-Sezer ◽

A Akdemir ◽

H Gurer-Orhan

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Antitumor Effects ◽

Antiestrogenic Activity ◽

Er Positive ◽

In Vivo Effects ◽

Mcf 7

Apigenin, a flavonoid, is reported to act as an estrogen receptor (ER) agonist and inhibit aromatase enzyme. However, amentoflavone, a biflavonoid bearing two apigenin molecules, has not been evaluated for its endocrine modulatory effects. Besides, it is highly consumed by young people to build muscles, enhance mood and lose weight. In the present study, apigenin was used as a reference molecule and ER mediated as well as ER-independent estrogenic/antiestrogenic activity of amentoflavone was investigated. Antitumor activity of amentoflavone was also investigated in both ER positive (MCF-7 BUS) and triple-negative (MDA-MB-231) breast cancer cells and its cytotoxicity was evaluated in human breast epithelial cells (MCF-10A). Our data confirmed ER agonist, aromatase inhibitory and cytotoxic effects of apigenin in breast cancer cells, where no ER mediated estrogenic effect and physiologically irrelevant, slight, aromatase inhibition was found for amentoflavone. Although selective cytotoxicity of amentoflavone was found in MCF-7 BUS cells, it does not seem to be an alternative to the present cytotoxic drugs. Therefore, neither an adverse effect, mediated by an estrogenic/antiestrogenic effect of amentoflavone nor a therapeutical benefit would be expected from amentoflavone. Further studies could be performed to investigate its in vivo effects.

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932 Targeting the 19S Proteasomal Subunit, Rpt4, in Colon Cancer Cells Induces Cell Death and Reduces Cellular Proliferation In Vitro and In Vivo

Gastroenterology ◽

10.1016/s0016-5085(13)60596-x ◽

2013 ◽

Vol 144 (5) ◽

pp. S-166-S-167

Author(s):

Karen Boland ◽

Caoimhin Concannon ◽

Niamh McCawley ◽

Elaine W. Kay ◽

Deborah McNamara ◽

...

Keyword(s):

Colon Cancer ◽

Cell Death ◽

Cancer Cells ◽

Cellular Proliferation ◽

Colon Cancer Cells ◽

Proliferation In Vitro

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TB-4 Antitumor effects of a novel curcumin derivative curcumin monoglucuronide on glioblastoma cells in vitro and in vivo

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab159.022 ◽

2021 ◽

Vol 3 (Supplement_6) ◽

pp. vi6-vi6

Author(s):

Takashi Fujii ◽

Shun Yamamuro ◽

Masamichi Takahashi ◽

Akihide Kondo ◽

Yoshitaka Narita ◽

...

Keyword(s):

Cell Death ◽

Water Soluble ◽

Dependent Manner ◽

Antitumor Effects ◽

Multiple Cell ◽

Human Gbm ◽

Dose Dependent ◽

Novel Therapeutic

Abstract The therapeutic outcome of glioblastomas (GBMs) is still very poor. Therefore, invention of novel therapeutic methods against GBM cases is considered urgent. The antitumor effects of naturally-derived compounds are attracting attention recently, and therapeutic efficacy of curcumin, a plant-derived compound previously used for multiple purpose, has been indicated in many cancer systems; however, clinical application of curcumin is considered difficult because of its poor bioavailability (under 1 %). Curcumin monoglucuronide (CMG), a water-soluble prodrug of curcumin recently developed for overcoming this weakness, has been demonstrated excellent antitumor effects for several malignancies in vitro and in vivo; therefore, we investigated the effects of CMG against GBM cells. CMG induced cell death of human GBM cells lines (T98G, U251MG, and U87MG) by dose dependent manner by triggering multiple forms of cell death such as apoptosis and perthanatos. Immunoblotting of CMG-treated GBM cell lysates demonstrated activation of multiple cell death signaling. Furthermore, immunodeficiency mice harboring intracerebral U87MG cell xenografts systemically treated by CMG showed significantly prolonged survival compared with control mice. These results suggest CMG would be a novel therapeutic agent against GBM cases.

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Antitumor effects of the small molecule DMAMCL in neuroblastoma via suppressing aerobic glycolysis and targeting PFKL

Cancer Cell International ◽

10.1186/s12935-021-02330-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Simeng Zhang ◽

Zhongyan Hua ◽

Gen Ba ◽

Ning Xu ◽

Jianing Miao ◽

...

Keyword(s):

Cell Death ◽

Synergistic Effects ◽

Aerobic Glycolysis ◽

Single Agent ◽

Molecular Compound ◽

Dependent Manner ◽

Antitumor Effects ◽

Atp Production

Abstract Background Neuroblastoma (NB) is a common solid malignancy in children that is associated with a poor prognosis. Although the novel small molecular compound Dimethylaminomicheliolide (DMAMCL) has been shown to induce cell death in some tumors, little is known about its role in NB. Methods We examined the effect of DMAMCL on four NB cell lines (NPG, AS, KCNR, BE2). Cellular confluence, survival, apoptosis, and glycolysis were detected using Incucyte ZOOM, CCK-8 assays, Annexin V-PE/7-AAD flow cytometry, and Seahorse XFe96, respectively. Synergistic effects between agents were evaluated using CompuSyn and the effect of DMAMCL in vivo was evaluated using a xenograft mouse model. Phosphofructokinase-1, liver type (PFKL) expression was up- and down-regulated using overexpression plasmids or siRNA. Results When administered as a single agent, DMAMCL decreased cell proliferation in a time- and dose-dependent manner, increased the percentage of cells in SubG1 phase, and induced apoptosis in vitro, as well as inhibiting tumor growth and prolonging survival in tumor-bearing mice (NGP, BE2) in vivo. In addition, DMAMCL exerted synergistic effects when combined with etoposide or cisplatin in vitro and displayed increased antitumor effects when combined with etoposide in vivo compared to either agent alone. Mechanistically, DMAMCL suppressed aerobic glycolysis by decreasing glucose consumption, lactate excretion, and ATP production, as well as reducing the expression of PFKL, a key glycolysis enzyme, in vitro and in vivo. Furthermore, PFKL overexpression attenuated DMAMCL-induced cell death, whereas PFKL silencing promoted NB cell death. Conclusions The results of this study suggest that DMAMCL exerts antitumor effects on NB both in vitro and in vivo by suppressing aerobic glycolysis and that PFKL could be a potential target of DMAMCL in NB.

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Immunomodulatory activity of IR700-labelled affibody targeting HER2

Cell Death and Disease ◽

10.1038/s41419-020-03077-6 ◽

2020 ◽

Vol 11 (10) ◽

Author(s):

Justyna Mączyńska ◽

Chiara Da Pieve ◽

Thomas A. Burley ◽

Florian Raes ◽

Anant Shah ◽

...

Keyword(s):

Cell Death ◽

Cancer Cells ◽

Light Irradiation ◽

Immunomodulatory Activity ◽

Her2 Positive ◽

Immunological Responses ◽

Cancer Cell Death ◽

Immature Dendritic Cells

Abstract There is an urgent need to develop therapeutic approaches that can increase the response rate to immuno-oncology agents. Photoimmunotherapy has recently been shown to generate anti-tumour immunological responses by releasing tumour-associated antigens from ablated tumour cell residues, thereby enhancing antigenicity and adjuvanticity. Here, we investigate the feasibility of a novel HER2-targeted affibody-based conjugate (ZHER2:2395-IR700) selectively to induce cancer cell death in vitro and in vivo. The studies in vitro confirmed the specificity of ZHER2:2395-IR700 binding to HER2-positive cells and its ability to produce reactive oxygen species upon light irradiation. A conjugate concentration- and light irradiation-dependent decrease in cell viability was also demonstrated. Furthermore, light-activated ZHER2:2395-IR700 triggered all hallmarks of immunogenic cell death, as defined by the translocation of calreticulin to the cell surface, and the secretion of ATP, HSP70/90 and HMGB1 from dying cancer cells into the medium. Irradiating a co-culture of immature dendritic cells (DCs) and cancer cells exposed to light-activated ZHER2:2395-IR700 enhanced DC maturation, as indicated by augmented expression of CD86 and HLA-DR. In SKOV-3 xenografts, the ZHER2:2395-IR700-based phototherapy delayed tumour growth and increased median overall survival. Collectively, our results strongly suggest that ZHER2:2395-IR700 is a promising new therapeutic conjugate that has great potential to be applicable for photoimmunotherapy-based regimens.

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Anticancer Activity of Cynomorium coccineum

Cancers ◽

10.3390/cancers10100354 ◽

2018 ◽

Vol 10 (10) ◽

pp. 354 ◽

Cited By ~ 7

Author(s):

Mouna Sdiri ◽

Xiangmin Li ◽

William Du ◽

Safia El-Bok ◽

Yi-Zhen Xie ◽

...

Keyword(s):

Cell Cycle ◽

Cell Death ◽

Anticancer Activity ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Cell Cycle Progression ◽

Cycle Progression

The extensive applications of Cynomorium species and their rich bioactive secondary metabolites have inspired many pharmacological investigations. Previous research has been conducted to examine the biological activities and numerous interesting pharmaceutical activities have been reported. However, the antitumor activities of these species are unclear. To understand the potential anticancer activity, we screened Cynomorium coccineum and Cynomorium songaricum using three different extracts of each species. In this study, the selected extracts were evaluated for their ability to decrease survival rates of five different cancer cell lines. We compared the cytotoxicity of the three different extracts to the anticancer drug vinblastine and one of the most well-known medicinal mushrooms Amaurederma rude. We found that the water and alcohol extracts of C. coccineum at the very low concentrations possessed very high capacity in decreasing the cancer cells viability with a potential inhibition of tumorigenesis. Based on these primitive data, we subsequently tested the ethanol and the water extracts of C. coccineum, respectively in in vitro and in vivo assays. Cell cycle progression and induction of programmed cell death were investigated at both biological and molecular levels to understand the mechanism of the antitumor inhibitory action of the C. coccineum. The in vitro experiments showed that the treated cancer cells formed fewer and smaller colonies than the untreated cells. Cell cycle progression was inhibited, and the ethanol extract of C. coccineum at a low concentration induced accumulation of cells in the G1 phase. We also found that the C. coccineum’s extracts suppressed viability of two murine cancer cell lines. In the in vivo experiments, we injected mice with murine cancer cell line B16, followed by peritoneal injection of the water extract. The treatment prolonged mouse survival significantly. The tumors grew at a slower rate than the control. Down-regulation of c-myc expression appeared to be associated with these effects. Further investigation showed that treatment with C. coccineum induced the overexpression of the tumor suppressor Foxo3 and other molecules involved in inducing autophagy. These results showed that the C. coccineum extract exerts its antiproliferative activity through the induction of cell death pathway. Thus, the Cynomorium plants appear to be a promising source of new antineoplastic compounds.

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Synergistic tumor inhibition of colon cancer cells by nitazoxanide and obeticholic acid, a farnesoid X receptor ligand

Cancer Gene Therapy ◽

10.1038/s41417-020-00239-8 ◽

2020 ◽

Author(s):

Junhui Yu ◽

Kui Yang ◽

Jianbao Zheng ◽

Wei Zhao ◽

Xuejun Sun

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Farnesoid X Receptor ◽

Colon Cancer Cells ◽

Antitumor Effects ◽

Colorectal Tumorigenesis ◽

Tumor Inhibition ◽

Combination Study

Abstract The tumor-suppressive role of Farnesoid X receptor (FXR) in colorectal tumorigenesis supports restoring FXR expression as a novel therapeutic strategy. However, the complicated signaling network and tumor heterogeneity hinder the effectiveness of FXR agonists in the clinical setting. These difficulties highlight the importance of identifying drug combinations with potency and specificity to enhance the antitumor effects of FXR agonists. In this study, we found that the β-catenin level affected the antitumor effects of the FXR agonist OCA on colon cancer cells. Mechanistic studies identified a novel FXR/β-catenin complex in colon cancer cells. Furthermore, the depletion of β-catenin expedited FXR nuclear localization and enhanced its occupancy of the SHP promoter and thereby sensitized colon cancer cells to OCA. Furthermore, we utilized a drug combination study and identified that the antiparasitic drug nitazoxanide (NTZ) abrogated β-catenin expression and acted synergistically with OCA in colon cancer cells. The combination of OCA plus NTZ exerts synergistic tumor inhibition in CRC both in vitro and in vivo by cooperatively upregulating SHP expression. In conclusion, our study offers useful evidence for the clinical use of FXR agonists combined with β-catenin inhibitors in combating CRC.

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Dominant-negative ATF5 rapidly depletes survivin in tumor cells

Cell Death and Disease ◽

10.1038/s41419-019-1872-y ◽

2019 ◽

Vol 10 (10) ◽

Author(s):

Xiaotian Sun ◽

James M. Angelastro ◽

David Merino ◽

Qing Zhou ◽

Markus D. Siegelin ◽

...

Keyword(s):

Cell Death ◽

Tumor Cell ◽

Cancer Cells ◽

Dominant Negative ◽

Tumor Cell Death ◽

Cell Penetrating ◽

Selective Death ◽

Tumor Types

Abstract Survivin (BIRC5, product of the BIRC5 gene) is highly expressed in many tumor types and has been widely identified as a potential target for cancer therapy. However, effective anti-survivin drugs remain to be developed. Here we report that both vector-delivered and cell-penetrating dominant-negative (dn) forms of the transcription factor ATF5 that promote selective death of cancer cells in vitro and in vivo cause survivin depletion in tumor cell lines of varying origins. dn-ATF5 decreases levels of both survivin mRNA and protein. The depletion of survivin protein appears to be driven at least in part by enhanced proteasomal turnover and depletion of the deubiquitinase USP9X. Survivin loss is rapid and precedes the onset of cell death triggered by dn-ATF5. Although survivin downregulation is sufficient to drive tumor cell death, survivin over-expression does not rescue cancer cells from dn-ATF5-promoted apoptosis. This indicates that dn-ATF5 kills malignant cells by multiple mechanisms that include, but are not limited to, survivin depletion. Cell-penetrating forms of dn-ATF5 are currently being developed for potential therapeutic use and the present findings suggest that they may pose an advantage over treatments that target only survivin.

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Cordycepin induces apoptosis in human tongue cancer cells in vitro and has antitumor effects in vivo

Archives of Oral Biology ◽

10.1016/j.archoralbio.2020.104846 ◽

2020 ◽

Vol 118 ◽

pp. 104846

Author(s):

Qingwei Zheng ◽

Jing Sun ◽

Wenli Li ◽

Shuangnan Li ◽

Kai Zhang

Keyword(s):

Cancer Cells ◽

Tongue Cancer ◽

Antitumor Effects ◽

Human Tongue

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Branched-chain amino acid aminotransferase 2 regulates ferroptotic cell death in cancer cells

Cell Death and Differentiation ◽

10.1038/s41418-020-00644-4 ◽

2020 ◽

Author(s):

Kang Wang ◽

Zhengyang Zhang ◽

Hsiang-i Tsai ◽

Yanfang Liu ◽

Jie Gao ◽

...

Keyword(s):

Cell Death ◽

Amino Acid ◽

Cancer Cells ◽

Ectopic Expression ◽

Branched Chain Amino Acid ◽

Pancreatic Cancer Cells ◽

Key Enzyme ◽

Branched Chain

Abstract Ferroptosis, a form of iron-dependent cell death driven by cellular metabolism and iron-dependent lipid peroxidation, has been implicated as a tumor-suppressor function for cancer therapy. Recent advance revealed that the sensitivity to ferroptosis is tightly linked to numerous biological processes, including metabolism of amino acid and the biosynthesis of glutathione. Here, by using a high-throughput CRISPR/Cas9-based genetic screen in HepG2 hepatocellular carcinoma cells to search for metabolic proteins inhibiting ferroptosis, we identified a branched-chain amino acid aminotransferase 2 (BCAT2) as a novel suppressor of ferroptosis. Mechanistically, ferroptosis inducers (erastin, sorafenib, and sulfasalazine) activated AMPK/SREBP1 signaling pathway through iron-dependent ferritinophagy, which in turn inhibited BCAT2 transcription. We further confirmed that BCAT2 as the key enzyme mediating the metabolism of sulfur amino acid, regulated intracellular glutamate level, whose activation by ectopic expression specifically antagonize system Xc– inhibition and protected liver and pancreatic cancer cells from ferroptosis in vitro and in vivo. On the contrary, direct inhibition of BCAT2 by RNA interference, or indirect inhibition by blocking system Xc– activity, triggers ferroptosis. Finally, our results demonstrate the synergistic effect of sorafenib and sulfasalazine in downregulating BCAT2 expression and dictating ferroptotic death, where BCAT2 can also be used to predict the responsiveness of cancer cells to ferroptosis-inducing therapies. Collectively, these findings identify a novel role of BCAT2 in ferroptosis, suggesting a potential therapeutic strategy for overcoming sorafenib resistance.

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