scholarly journals Selective imaging and cancer cell death via pH switchable near-infrared fluorescence and photothermal effects

2016 ◽  
Vol 7 (9) ◽  
pp. 5995-6005 ◽  
Author(s):  
Jingye Zhang ◽  
Zining Liu ◽  
Peng Lian ◽  
Jun Qian ◽  
Xinwei Li ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Near Infrared ◽  
Near Infrared Fluorescence ◽  
Ph Changes ◽  
Cancer Cell Death ◽  
Photothermal Effects

A theranostic probe is designed that specifically illuminates and photoablates cancer cells by sensing pH changes in the lysosomes and mitochondria.

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

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,...

scholarly journals Mitochondrial Complex I Inhibitors and Forced Oxidative Phosphorylation Synergize in Inducing Cancer Cell Death

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Roberta Palorini ◽  
Tiziana Simonetto ◽  
Claudia Cirulli ◽  
Ferdinando Chiaradonna
Keyword(s):  
Cell Death ◽  
Oxidative Phosphorylation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Complex I ◽  
Mitochondrial Complex I ◽  
Low Doses ◽  
Mitochondrial Complex ◽  
Cancer Cell Death ◽  
Glucose Depletion

Cancer cells generally rely mostly on glycolysis rather than oxidative phosphorylation (OXPHOS) for ATP production. In fact, they are particularly sensitive to glycolysis inhibition and glucose depletion. On the other hand mitochondrial dysfunctions, involved in the onset of the Warburg effect, are sometimes also associated with the resistance to apoptosis that characterizes cancer cells. Therefore, combined treatments targeting both glycolysis and mitochondria function, exploiting peculiar tumor features, might be lethal for cancer cells. In this study, we show that glucose deprivation and mitochondrial Complex I inhibitors synergize in inducing cancer cell death. In particular, our results reveal that low doses of Complex I inhibitors, ineffective on immortalized cells and in high glucose growth, become specifically cytotoxic on cancer cells deprived of glucose. Importantly, the cytotoxic effect of the inhibitors on cancer cells is strongly enhanced by forskolin, a PKA pathway activator, that we have previously shown to stimulate OXPHOS. Taken together, we demonstrate that induction in cancer cells of a switch from a glycolytic to a more respirative metabolism, obtained by glucose depletion or mitochondrial activity stimulation, strongly increases their sensitivity to low doses of mitochondrial Complex I inhibitors. Our findings might be a valuable approach to eradicate cancer cells.

scholarly journals Targeted Depletion of Amino Acids As a Novel Therapy for Acute Leukemia and Other Cancers: Mechanisms and Countermechanisms

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4716-4716 ◽  
Author(s):  
Aysenur Esen ◽  
Anwar A Khan ◽  
Jason Chan ◽  
Nadim Mahmud ◽  
John G. Quigley
Keyword(s):  
Amino Acids ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Stress Responses ◽  
Drug Combination ◽  
Metabolic Reprogramming ◽  
Low Doses ◽  
Cancer Cell Death ◽  
Mtorc1 Pathway

Abstract Introduction: Metabolic reprogramming by cancer cells to allow proliferation and survival suggests targeting of relatively cancer cell-specific metabolic processes as a potential cancer therapy. The amino acid (aa) glutamine (GLN) functions as an exchange factor to facilitate cell import of essential amino acids (EAA), which positively regulate translation by the mTORC1 pathway (via phosphorylation of S70K and 4EBP1), allowing proliferation. Most cancer cells also rely on GLN, rather than glucose for citric acid cycle (TCA) anaplerosis, and as a source of energy, anti-oxidants and components for protein synthesis. L-asparaginase (L-Ase), an enzyme that breaks down extracellular asparagine (ASN, the least prevalent intracellular aa), is used in the treatment of ALL. L-Ase is also glutaminolytic, resulting in GLN depletion and apoptosis that is suppressed by ASN repletion, which modulates the cell stress responses (ISR, upregulatingATF4, CHOP, aa transporters, and asparagine synthetase (ASNS)). Thus, (i) ASN is a critical signal preventing cell death from GLN depletion; (ii) ASN repletion (via ASNS) may be the important function of GLN within cancer cells, and (iii) mechanisms that deplete bothkey aa may be synergistic in implementing cancer cell death Apart from non-EAA synthesis and aa uptake (#1 in Fig. 1A), there are two major pathways of cellular aa repletion: (i) autophagy, a process whereby damaged proteins are delivered to the lysosome for degradation (#2), and (ii) the ubiquitin-proteasome system (UPS, #3), which also degrades damaged or misfolded cell proteins, allowing aa recycling. Notably, UPS inhibition significantly decreases ASN (andcystine) levels. The aim of our studies is to explore mechanisms of depleting intracellular GLN and ASN levels in cancer cells, firstinvestigating the potential synergistic effects of combining L-Ase, with Chloroquine (CQ, autophagy inhibition) and Bortezomib (BTZ, proteasome inhibition), and then analyzing cancer cell counter mechanisms. Results: We performed kill-curves with individual drugs, and then combinations of L-ase, CQ and BTZ in REH (ALL) cells. Notably, inhibitory effects on aarepletion pathways, as determined by western blot analysis of cell lysates at 12h (Fig. 1B), were seen with a combination of significantly lowered doses of each drug [BTZ 2nM (40% of LD50); L-Ase 0.2IU (15%); CQ 100mM (50%)]. The mTORC1 pathway is especially susceptible to inhibition by drug combination-mediated aa depletion (decreased phosphorylation of 4EBP1 and S6K1; compare lanes 2-4 & 5-8), while autophagy (monitored by increasing levels of LC3-II) is also inhibited. Cell viability was assessed after 48h. Although the low doses of each drug used has a minimal impact on viability (range 75-130% of control), the combination above (2nM;0.2IU;100mM) results in synergistic cell death [55% (n = 1)]. We will examine further the effects of this drug combination on normal CD34+ cells, prior to studies of efficacy inxeno-transplant models. Most tumors are metabolically flexible, e.g., they can use glucose if deprived of GLN to replenish TCA, and, via TCA intermediates, increase GLN levels, and thereby ASN, via pyruvate carboxylase (PC), transaminases (GOT1, 2), glutaminesynthetases(GDH, GS) and ASNS (see Fig. 1 pathways). Thus, we interrogated, byqPCR, potentially relevant pathways that may be used to evade glutamine and asparagine depletion-induced apoptosis (Fig. 1C). Of 12 genes tested, GLN deprivation significantlyupregulatesGLS1, GOT1, and ASNS to increase ASN levels, while the ISR is activated (CHOP), and SLC7A11, a cysteine importer upregulated in tumors (for glutathione production) is also significantly upregulated. Preliminary studies of REH and A549 (lung cancer) cells suggest a common theme in metabolic responses to GLN depletion in diverse cancer cells is ASN synthesis through GOT1 and ASNS upregulation, and likely ROS production throughcystineuptake. Conclusions: Commonly, inhibition of one metabolic pathway results in upregulation of another. Our studies indicate that combination therapy, using low doses of available, well-studied drugs depletes keyaa ASN and GLN, and prevents their repletion, causing cancer cell death. In addition, our studies of the cellular responses to GLN depletion alone indicate additional targets that should be considered to prevent ASN-mediated inhibition of cell death in diverse cancer types. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Fluorinated thiazolidinols cause cell death in A549 lung cancer cells via PI3K/AKT/mTOR and MAPK/ERK signalling pathways

MedChemComm ◽  
2016 ◽  
Vol 7 (6) ◽  
pp. 1197-1203 ◽  
Author(s):  
Ravindra M. Kumbhare ◽  
Tulshiram L. Dadmal ◽  
Dinesh Kumar ◽  
M. Janaki Ramaiah ◽  
Anudeep Kota ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Lung Cancer Cells ◽  
Signalling Pathways ◽  
Lung Cancer Cell ◽  
Cancer Cell Death ◽  
A549 Lung Cancer Cell ◽  
A549 Lung

Fluorinated thiazolidinols cause A549 lung cancer cell death by acting via PI3K/Akt/mTOR and MEK/ERK pathways.

New Fe(iii) and Co(ii) salen complexes with pendant distamycins: selective targeting of cancer cells by DNA damage and mitochondrial pathways

2016 ◽  
Vol 45 (22) ◽  
pp. 9345-9353 ◽  
Author(s):  
Asfa Ali ◽  
Mohini Kamra ◽  
Arunoday Bhan ◽  
Subhrangsu S. Mandal ◽  
Santanu Bhattacharya
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Metal Complexes ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cancer Cell Death ◽  
Salen Complexes ◽  
Selective Targeting

Distamycin like moieties conjugated with core Fe(iii) and Co(ii) based salens were synthesized and studied. The metal complexes showed better and differential activity toward cancer cell death.

Tripeptide consisting of benzyl protected di-cysteine and phenylalanine forms spherical assembly and induces cytotoxicity in cancer cells via apoptosis

RSC Advances ◽  
2016 ◽  
Vol 6 (113) ◽  
pp. 112667-112676 ◽  
Author(s):  
Biswadip Banerji ◽  
Moumita Chatterjee ◽  
Chandraday Prodhan ◽  
Keya Chaudhuri
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Growth Medium ◽  
Cancer Cell Death

Tripeptide self assemblies in cell growth medium induce apoptosis and promoting cancer cell death at submicromolar concentration.

scholarly journals GPR55 Receptor Activation by the N-Acyl Dopamine Family Lipids Induces Apoptosis in Cancer Cells via the Nitric Oxide Synthase (nNOS) Over-Stimulation

2021 ◽  
Vol 22 (2) ◽  
pp. 622
Author(s):  
Mikhail G. Akimov ◽  
Alina M. Gamisonia ◽  
Polina V. Dudina ◽  
Natalia M. Gretskaya ◽  
Anastasia A. Gaydaryova ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Death ◽  
Nitric Oxide Synthase ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Receptor Activation ◽  
Gene Expression Measurement ◽  
Fatty Acid Amides ◽  
Cancer Cell Death ◽  
Oxide Synthase

GPR55 is a GPCR of the non-CB1/CB2 cannabinoid receptor family, which is activated by lysophosphatidylinositol (LPI) and stimulates the proliferation of cancer cells. Anandamide, a bioactive lipid endocannabinoid, acts as a biased agonist of GPR55 and induces cancer cell death, but is unstable and psychoactive. We hypothesized that other endocannabinoids and structurally similar compounds, which are more hydrolytically stable, could also induce cancer cell death via GPR55 activation. We chemically synthesized and tested a set of fatty acid amides and esters for cell death induction via GPR55 activation. The most active compounds appeared to be N-acyl dopamines, especially N-docosahexaenoyl dopamine (DHA-DA). Using a panel of cancer cell lines and a set of receptor and intracellular signal transduction machinery inhibitors together with cell viability, Ca2+, NO, ROS (reactive oxygen species) and gene expression measurement, we showed for the first time that for these compounds, the mechanism of cell death induction differed from that published for anandamide and included neuronal nitric oxide synthase (nNOS) overstimulation with concomitant oxidative stress induction. The combination of DHA-DA with LPI, which normally stimulates cancer proliferation and is increased in cancer setting, had an increased cytotoxicity for the cancer cells indicating a therapeutic potential.

scholarly journals Salubrinal Enhances Cancer Cell Death during Glucose Deprivation through the Upregulation of xCT and Mitochondrial Oxidative Stress

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1101
Author(s):  
Mei-Chun Chen ◽  
Li-Lin Hsu ◽  
Sheng-Fan Wang ◽  
Yi-Ling Pan ◽  
Jeng-Fan Lo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Redox Homeostasis ◽  
Glucose Deprivation ◽  
Metabolic Flexibility ◽  
Mitochondrial Oxidative Stress ◽  
Cancer Cell Death ◽  
Adaptation Response

Cancer cells have the metabolic flexibility to adapt to heterogeneous tumor microenvironments. The integrated stress response (ISR) regulates the cellular adaptation response during nutrient stress. However, the issue of how the ISR regulates metabolic flexibility is still poorly understood. In this study, we activated the ISR using salubrinal in cancer cells and found that salubrinal repressed cell growth, colony formation, and migration but did not induce cell death in a glucose-containing condition. Under a glucose-deprivation condition, salubrinal induced cell death and increased the levels of mitochondrial reactive oxygen species (ROS). We found that these effects of salubrinal and glucose deprivation were associated with the upregulation of xCT (SLC7A11), which functions as an antiporter of cystine and glutamate and maintains the level of glutathione to maintain redox homeostasis. The upregulation of xCT did not protect cells from oxidative stress-mediated cell death but promoted it during glucose deprivation. In addition, the supplementation of ROS scavenger N-acetylcysteine and the maintenance of intracellular levels of amino acids via sulfasalazine (xCT inhibitor) or dimethyl-α-ketoglutarate decreased the levels of mitochondrial ROS and protected cells from death. Our results suggested that salubrinal enhances cancer cell death during glucose deprivation through the upregulation of xCT and mitochondrial oxidative stress.

scholarly journals RAS-related GTPases DIRAS1 and DIRAS2 induce autophagic cancer cell death and are required for autophagy in murine ovarian cancer cells

Autophagy ◽  
2018 ◽  
Vol 14 (4) ◽  
pp. 637-653 ◽  
Author(s):  
Margie N. Sutton ◽  
Hailing Yang ◽  
Gilbert Y. Huang ◽  
Caroline Fu ◽  
Michael Pontikos ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Ovarian Cancer Cells ◽  
Cancer Cell Death

scholarly journals Evaluating Nanoshells and a Potent Biladiene Photosensitizer for Dual Photothermal and Photodynamic Therapy of Triple Negative Breast Cancer Cells

Nanomaterials ◽  
2018 ◽  
Vol 8 (9) ◽  
pp. 658 ◽  
Author(s):  
Rachel Riley ◽  
Rachel O’Sullivan ◽  
Andrea Potocny ◽  
Joel Rosenthal ◽  
Emily Day
Keyword(s):  
Breast Cancer ◽  
Cell Death ◽  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Gold Shell ◽  
Cancer Cell Death ◽  
Silica Core

Light-activated therapies are ideal for treating cancer because they are non-invasive and highly specific to the area of light application. Photothermal therapy (PTT) and photodynamic therapy (PDT) are two types of light-activated therapies that show great promise for treating solid tumors. In PTT, nanoparticles embedded within tumors emit heat in response to laser light that induces cancer cell death. In PDT, photosensitizers introduced to the diseased tissue transfer the absorbed light energy to nearby ground state molecular oxygen to produce singlet oxygen, which is a potent reactive oxygen species (ROS) that is toxic to cancer cells. Although PTT and PDT have been extensively evaluated as independent therapeutic strategies, they each face limitations that hinder their overall success. To overcome these limitations, we evaluated a dual PTT/PDT strategy for treatment of triple negative breast cancer (TNBC) cells mediated by a powerful combination of silica core/gold shell nanoshells (NSs) and palladium 10,10-dimethyl-5,15-bis(pentafluorophenyl)biladiene-based (Pd[DMBil1]-PEG750) photosensitizers (PSs), which enable PTT and PDT, respectively. We found that dual therapy works synergistically to induce more cell death than either therapy alone. Further, we determined that low doses of light can be applied in this approach to primarily induce apoptotic cell death, which is vastly preferred over necrotic cell death. Together, our results show that dual PTT/PDT using silica core/gold shell NSs and Pd[DMBil1]-PEG750 PSs is a comprehensive therapeutic strategy to non-invasively induce apoptotic cancer cell death.

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