The Effects of the Surface Properties of a Gold Nanorod on Its In Vitro/Vivo Toxicity Against Cancer Cells

Gold nano rods (GNRs) have showed cytotoxicity to cancer cells. At the same time, it shows little effects on non-tumor cells. Between GNRs and sub-cellular organelles, the understanding of interaction plays a very important role to determine the intracellular mechanisms. The purpose of what we done is to explain the effects of the surface properties of GNRs on specific cancer cell death. Three GNR samples with different aspect ratios were finely prepared by the seed-mediated growth method. Then the intracellular transport and the in vitro/vivo mechanisms of cancer cell death were studied by transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), laser light scattering, and flow cytometry (FCM). It was found that GNRs700 exhibited the largest photothermal conversion efficiency. However, the GNR660 with or without light stimulation exhibited the highest cytotoxicity against cancer cells, which was contradict to the general knowledge. Detailed intracellular investigations showed that the lysosome was the key sub-organelle affecting the GNR function. Further experiments revealed that cytotoxicity was strongly affected by the GNR's surface potential. This potential was actually related to the density of surface cationic molecules, which further regulated lysosomal membrane penetration. The results obtained herein indicated that the physicochemical properties of the surface potential mediated the specific toxicity of GNRs against tumours.

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ATL

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000065 ◽

2014 ◽

Vol 24 (3) ◽

pp. 437-443 ◽

Cited By ~ 14

Author(s):

Jie Li ◽

Geng Cui ◽

Lu Sun ◽

Shu-Juan Wang ◽

Shuang Tian ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cell Death ◽

Epithelial Ovarian Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Apoptosis ◽

Cancer Cell Death ◽

Ovarian Cells

ObjectiveARHIis a maternally imprinted tumor suppressor gene that is responsible for initiating programmed cell death and inhibiting cancer cell growth. However, the influence ofARHIon epithelial ovarian cancer cell death and the underlying mechanisms behind howARHIregulates cancer cells still require further studies.MethodsEpithelial ovarian cancer cells TOV112D and ES-2 were used in this in vitro study. Cell proliferation, apoptosis, and autophagy activities were compared in TOV112D and ES-2 cells transfected withARHIvectors or control vectors. Bcl-2 siRNA was transfected into TOV112D cells to investigate the roles of Bcl-2 played in regulating apoptosis and autophagy.ResultsARHIexpression was reduced in TOV112D and ES-2 cells compared with normal epithelial ovarian cells (NOE095 and HOSEpiC). OverexpressedARHIinhibited cancer cell proliferation, whereas induced forced cell apoptosis and excessive formation of autophagosomes inhibited promoted cell death. Furthermore, we found that Bcl-2 expression moderately declined in response toARHIoverexpressing in ES-2 and TOV112D cells; meanwhile, more apoptotic cells and higher LC3 level presented after silence of Bcl-2 in TOV112D cells. Reduced Bcl-2–Beclin 1 complex were observed inARHIoverexpressing cells. Moreover, modulation ofARHIto Bcl-2 expression could be ascribed partially to the activation of PI3k/AKT pathway. The addition of LY294002 enabled to suppress Bcl-2 expression and cell proliferation.ConclusionsThe silence ofARHIexpression in vitro seems to accelerate the malignant transformation of healthy ovarian cells by restraining apoptosis and autophagy. The overexpressedARHIin TOV112D cancer cells suppresses the activation of PI3K/AKT and reduces the expression of Bcl-2, leading to enhanced cell apoptosis and autophagic cancer cell death.

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Synthesis, cellular evaluation, and mechanism of action of piperlongumine analogs

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1212802109 ◽

2012 ◽

Vol 109 (38) ◽

pp. 15115-15120 ◽

Cited By ~ 137

Author(s):

Drew J. Adams ◽

Mingji Dai ◽

Giovanni Pellegrino ◽

Bridget K. Wagner ◽

Andrew M. Stern ◽

...

Keyword(s):

Cell Death ◽

Cancer Cells ◽

Cancer Cell ◽

Mechanism Of Action ◽

Cell Types ◽

Structural Modifications ◽

Cancer Cell Death ◽

Nontransformed Cell

Piperlongumine is a naturally occurring small molecule recently identified to be toxic selectively to cancer cells in vitro and in vivo. This compound was found to elevate cellular levels of reactive oxygen species (ROS) selectively in cancer cell lines. The synthesis of 80 piperlongumine analogs has revealed structural modifications that retain, enhance, and ablate key piperlongumine-associated effects on cells, including elevation of ROS, cancer cell death, and selectivity for cancer cells over nontransformed cell types. Structure/activity relationships suggest that the electrophilicity of the C2-C3 olefin is critical for the observed effects on cells. Furthermore, we show that analogs lacking a reactive C7-C8 olefin can elevate ROS to levels observed with piperlongumine but show markedly reduced cell death, suggesting that ROS-independent mechanisms, including cellular cross-linking events, may also contribute to piperlongumine’s induction of apoptosis. In particular, we have identified irreversible protein glutathionylation as a process associated with cellular toxicity. We propose a mechanism of action for piperlongumine that may be relevant to other small molecules having two sites of reactivity, one with greater and the other with lesser electrophilicity.

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The Azurin-Derived Peptide CT-p19LC Exhibits Membrane-Active Properties and Induces Cancer Cell Death

Biomedicines ◽

10.3390/biomedicines9091194 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1194

Author(s):

Ana Rita Garizo ◽

Lígia F. Coelho ◽

Sandra Pinto ◽

Tiago P. Dias ◽

Fábio Fernandes ◽

...

Keyword(s):

Cell Death ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Total Charge ◽

Cancer Cell Death ◽

Proliferation And Apoptosis ◽

Mcf 7

Peptides have been thoroughly studied as new therapeutic strategies for cancer treatment. In this work, we explored in vitro the anticancer potential of three novel peptides derived from the C-terminal of azurin, an anticancer bacterial protein produced by Pseudomonas aeruginosa. CT-p26, CT-p19 and CT-p19LC peptides were previously obtained through an in silico peptide design optimization process, CT-p19LC being the most promising as it presented higher hydrophobicity and solubility, positive total charge and, most importantly, greater propensity for anticancer activity. Therefore, in this study, through proliferation and apoptosis assays, CT-p19LC was tested in four cancer cell lines—A549, MCF-7, HeLa and HT-29—and in two non-cancer cell lines—16HBE14o- and MCF10A. Its membrane-targeting activity was further evaluated with zeta potential measurements and membrane order was assessed with the Laurdan probe. The results obtained demonstrated that CT-p19LC decreases cell viability through induction of cell death and binds to the plasma membrane of cancer cells, but not to non-cancer cells, making them less rigid. Overall, this study reveals that CT-p19LC is an auspicious selective anticancer peptide able to react with cancer cell membranes and cause effective action.

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Magneto Mitochondrial Dysfunction Mediated Cancer Cell Death Using Intracellular Magnetic Nano-Transducers

Biomaterials Science ◽

10.1039/d1bm00419k ◽

2021 ◽

Author(s):

Wooram Park ◽

Seok-Jo Kim ◽

Paul Cheresh ◽

Jeanho Yun ◽

Byeongdu Lee ◽

...

Keyword(s):

Cell Death ◽

Cancer Therapy ◽

Mitochondrial Dysfunction ◽

Cancer Cells ◽

Cancer Cell ◽

High Sensitivity ◽

Intrinsic Pathway ◽

Cancer Cell Death

Mitochondria are crucial regulators of the intrinsic pathway of cancer cell death. The high sensitivity of cancer cells to mitochondrial dysfunction offers opportunities for emerging targets in cancer therapy. Herein,...

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Hydrogen Phosphate Selectively Induces MDA-MB-231 Breast Cancer Cell Death in vitro

10.21203/rs.3.rs-956711/v1 ◽

2021 ◽

Author(s):

Aya Shanti ◽

Kenana Al Adem ◽

Cesare Stefanini ◽

Sungmun Lee

Keyword(s):

Breast Cancer ◽

Cell Death ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Dihydrogen Phosphate ◽

Human Breast ◽

Hydrogen Phosphate ◽

Cancer Cell Death ◽

Phosphate Ions

Abstract Phosphate ions are the most abundant anions inside the cells, and they are increasingly gaining attention as key modulators of cellular function and gene expression. However, little is known about the effect of inorganic phosphate ions on cancer cells, particularly breast cancer cells. Here, we investigated the toxicity of different phosphate compounds to triple-negative human breast cancer cells (MDA-MB-231) and compared it to that of human monocytes (THP-1). We found that, unlike dihydrogen phosphate (H2PO4−), hydrogen phosphate (HPO42−) at 20 mM or lower concentrations induced breast cancer (MDA-MB-231) cell death more than immune (THP-1) cell death. We correlate this effect to the fact that phosphate in the form of HPO42− raises pH levels to alkaline levels which are not optimum for transport of phosphate into cancer cells. The results in this study highlight the importance of further exploring hydrogen phosphate (HPO42−) as a potential therapeutic for the treatment of breast cancer.

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Thiol antioxidants sensitize malabaricone C induced cancer cell death via reprogramming redox sensitive p53 and NF-κB proteins in vitro and in vivo

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2020.01.011 ◽

2020 ◽

Vol 148 ◽

pp. 182-199

Author(s):

Mrityunjay Tyagi ◽

Ajay Kumar Bauri ◽

Subrata Chattopadhyay ◽

Birija Sankar Patro

Keyword(s):

Cell Death ◽

Cancer Cell ◽

Cancer Cell Death

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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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