scholarly journals Glucose Limitation Sensitizes Cancer Cells to Selenite-Induced Cytotoxicity via SLC7A11-Mediated Redox Collapse

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 345
Author(s):  
Hui Chen ◽  
Han Zhang ◽  
Lixing Cao ◽  
Jinling Cui ◽  
Xuan Ma ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cytotoxic Effect ◽  
Therapeutic Window ◽  
Intermittent Fasting ◽  
Oxygen Species ◽  
Glucose Limitation ◽  
Anti Cancer ◽  
Xenograft Models

Combination of intermittent fasting and chemotherapy has been drawn an increasing attention because of the encouraging efficacy. In this study, we evaluated the anti-cancer effect of combination of glucose limitation and selenite (Se), a representative inorganic form of selenium, that is preferentially accumulated in tumors. Results showed that cytotoxic effect of selenite on cancer cells, but not on normal cells, was significantly enhanced in response to the combination of selenite and glucose limitation. Furthermore, in vivo therapeutic efficacy of combining selenite with fasting was dramatically improved in xenograft models of lung and colon cancer. Mechanistically, we found that SLC7A11 expression in cancer cells was up-regulated by selenite both in vitro and in vivo. The elevated SLC7A11 led to cystine accumulation, NADPH depletion and the conversion of cystine to cysteine inhibition, which in turn boosted selenite-mediated reactive oxygen species (ROS), followed by enhancement of selenite-mediated cytotoxic effect. The findings of the present study provide an effective and practical approach for increasing the therapeutic window of selenite and imply that combination of selenite and fasting holds promising potential to be developed a clinically useful regimen for treating certain types of cancer.

scholarly journals Glucose Limitation Sensitizes Cancer Cells to Selenite-Induced Cytotoxic Effect via SLC7A11-Mediated Redox Collapse

2021 ◽  
Author(s):  
Hui Chen ◽  
Han Zhang ◽  
Lixing Cao ◽  
Jinling Cui ◽  
Xuan Ma ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cytotoxic Effect ◽  
Glucose Deprivation ◽  
Therapeutic Window ◽  
Glucose Starvation ◽  
Glucose Limitation ◽  
Elevated Expression ◽  
Xenograft Models

Abstract Background: Combination of fasting with chemotherapy has been drawn an increasing attention because of the encouraging efficacy. SLC7A11 is frequently over-expressed in most of cancer cells, and elevated expression of SLC7A11 renders cancer cells more susceptible to glucose starvation owing to SLC7A11-mediated redox collapse. Selenite is a representative inorganic form of selenium, and is preferentially accumulated in tumors. This selenophilic peculiarity of cancer cells is closely associated with the elevated expression of SLC7A11. Given the established the link among glucose deprivation, SLC7A11, oxidative stress and selenite, we hypothesized that glucose starvation could specifically sensitize cancer cells to selenite-mediated cytotoxic effect. Methods: The cytotoxic effect of combining selenite with glucose starvation on cancer cell was assessed by crystal violet staining and Annexin V/PI staining. Flow cytometry were employed to assess intracellular ROS levels, labile iron pool and lipid peroxidation. Xenograft models were used to test its in vivo antitumor activity. Commercial assay kit, LC-MS, RNA interference and western blot were applied to investigate the mechanism underlying synergistic effect.Results: It showed that cytotoxic effect of selenite on cancer cells, but not on normal cells, was significantly enhanced in response to the combination of selenite and glucose limitation. Furthermore, in vivo therapeutic efficacy of combining selenite with fasting was dramatically improved in xenograft models of lung and colon cancer. Mechanistically, we found that SLC7A11 expression in cancer cells was up-regulated by selenite both in vitro and in vivo. The elevated SLC7A11 led to accumulation of cystine, depletion of NADPH, and inhibition of cystine to cysteine conversion, which in turn boosted selenite-mediated reactive oxygen species (ROS), followed by enhancement of selenite-mediated cytotoxic effect. Conclusion: The findings of the present study provide an effective and practical approach for increasing the therapeutic window of selenite, and imply that combination of selenite with fasting holds promising potential to be developed a clinically useful regimen for treating certain types of cancer.

scholarly journals Doxorubicin loaded magnetism nanoparticles based on cyclodextrin dendritic-graphene oxide inhibited MCF-7 cell proliferation

2021 ◽  
Vol 12 (1) ◽  
pp. 8-15
Author(s):  
Ainaz Mihanfar ◽  
Niloufar Targhazeh ◽  
Shirin Sadighparvar ◽  
Saber Ghazizadeh Darband ◽  
Maryam Majidinia ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Anticancer Drug Delivery ◽  
Release Studies ◽  
Anti Cancer ◽  
Acidic Conditions ◽  
Mcf 7

Abstract Doxorubicin (DOX) is an effective chemotherapeutic agent used for the treatment of various types of cancer. However, its poor solubility, undesirable side effects, and short half-life have remained a challenge. We used a formulation based on graphene oxide as an anticancer drug delivery system for DOX in MCF-7 breast cancer cells, to address these issues. In vitro release studies confirmed that the synthesized formulation has an improved release profile in acidic conditions (similar to the tumor microenvironment). Further in vitro studies, including MTT, uptake, and apoptosis assays were performed. The toxic effects of the nanocarrier on the kidney, heart and liver of healthy rats were also evaluated. We observed that the DOX-loaded carrier improved the cytotoxic effect of DOX on the breast cell line compared to free DOX. In summary, our results introduce the DOX-loaded carrier as a potential platform for in vitro targeting of cancer cells and suggest further studies are necessary to investigate its in vivo anti-cancer potential.

scholarly journals Resolvin D1 reduces cancer growth stimulating a protective neutrophil-dependent recruitment of anti-tumor monocytes

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Domenico Mattoscio ◽  
Elisa Isopi ◽  
Alessia Lamolinara ◽  
Sara Patruno ◽  
Alessandro Medda ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Growth Curve ◽  
Immune Cells ◽  
Cancer Growth ◽  
Resolvin D1 ◽  
Anti Cancer ◽  
Classical Monocytes ◽  
Human And Mouse

Abstract Background Innovative therapies to target tumor-associated neutrophils (PMN) are of clinical interest, since these cells are centrally involved in cancer inflammation and tumor progression. Resolvin D1 (RvD1) is a lipid autacoid that promotes resolution of inflammation by regulating the activity of distinct immune and non-immune cells. Here, using human papilloma virus (HPV) tumorigenesis as a model, we investigated whether RvD1 modulates PMN to reduce tumor progression. Methods Growth-curve assays with multiple cell lines and in vivo grafting of two distinct HPV-positive cells in syngeneic mice were used to determine if RvD1 reduced cancer growth. To investigate if and how RvD1 modulates PMN activities, RNA sequencing and multiplex cytokine ELISA of human PMN in co-culture with HPV-positive cells, coupled with pharmacological depletion of PMN in vivo, were performed. The mouse intratumoral immune cell composition was evaluated through FACS analysis. Growth-curve assays and in vivo pharmacological depletion were used to evaluate anti-tumor activities of human and mouse monocytes, respectively. Bioinformatic analysis of The Cancer Genome Atlas (TCGA) database was exploited to validate experimental findings in patients. Results RvD1 decreased in vitro and in vivo proliferation of human and mouse HPV-positive cancer cells through stimulation of PMN anti-tumor activities. In addition, RvD1 stimulated a PMN-dependent recruitment of classical monocytes as key determinant to reduce tumor growth in vivo. In human in vitro systems, exposure of PMN to RvD1 increased the production of the monocyte chemoattractant protein-1 (MCP-1), and enhanced transmigration of classical monocytes, with potent anti-tumor actions, toward HPV-positive cancer cells. Consistently, mining of immune cells infiltration levels in cervical cancer patients from the TCGA database evidenced an enhanced immune reaction and better clinical outcomes in patients with higher intratumoral monocytes as compared to patients with higher PMN infiltration. Conclusions RvD1 reduces cancer growth by activating PMN anti-cancer activities and encouraging a protective PMN-dependent recruitment of anti-tumor monocytes. These findings demonstrate efficacy of RvD1 as an innovative therapeutic able to stimulate PMN reprogramming to an anti-cancer phenotype that restrains tumor growth.

scholarly journals Spironolactone, a Classic Potassium-Sparing Diuretic, Reduces Survivin Expression and Chemosensitizes Cancer Cells to Non-DNA-Damaging Anticancer Drugs

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1550 ◽  
Author(s):  
Tomomi Sanomachi ◽  
Shuhei Suzuki ◽  
Keita Togashi ◽  
Asuka Sugai ◽  
Shizuka Seino ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Kinase Inhibitors ◽  
Xenograft Model ◽  
Growth Factor Receptor ◽  
Survivin Expression ◽  
Mouse Xenograft Model ◽  
Anti Cancer ◽  
Underlying Mechanisms

Spironolactone, a classical diuretic drug, is used to treat tumor-associated complications in cancer patients. Spironolactone was recently reported to exert anti-cancer effects by suppressing DNA damage repair. However, it currently remains unclear whether spironolactone exerts combinational effects with non-DNA-damaging anti-cancer drugs, such as gemcitabine and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Using the cancer cells of lung cancer, pancreatic cancer, and glioblastoma, the combinational effects of spironolactone with gemcitabine and osimertinib, a third-generation EGFR-TKI, were examined in vitro with cell viability assays. To elucidate the underlying mechanisms, we investigated alterations induced in survivin, an anti-apoptotic protein, by spironolactone as well as the chemosensitization effects of the suppression of survivin by YM155, an inhibitor of survivin, and siRNA. We also examined the combinational effects in a mouse xenograft model. The results obtained revealed that spironolactone augmented cell death and the suppression of cell growth by gemcitabine and osimertinib. Spironolactone also reduced the expression of survivin in these cells, and the pharmacological and genetic suppression of survivin sensitized cells to gemcitabine and osimertinib. This combination also significantly suppressed tumor growth without apparent adverse effects in vivo. In conclusion, spironolactone is a safe candidate drug that exerts anti-cancer effects in combination with non-DNA-damaging drugs, such as gemcitabine and osimertinib, most likely through the suppression of survivin.

scholarly journals Two-stage nanoparticle delivery of piperlongumine and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) anti-cancer therapy

TECHNOLOGY ◽  
2016 ◽  
Vol 04 (01) ◽  
pp. 60-69 ◽  
Author(s):  
Charles C. Sharkey ◽  
Jiahe Li ◽  
Sweta Roy ◽  
Qianhui Wu ◽  
Michael R. King
Keyword(s):  
Cancer Cells ◽  
Survival Rates ◽  
Xenograft Model ◽  
Plga Nanoparticles ◽  
Mouse Xenograft Model ◽  
Anti Cancer ◽  
In Vivo Testing ◽  
Hct116 Cells

This study outlines a drug delivery mechanism that utilizes two independent vehicles, allowing for delivery of chemically and physically distinct agents. The mechanism was utilized to deliver a new anti-cancer combination therapy consisting of piperlongumine (PL) and TRAIL to treat PC3 prostate cancer and HCT116 colon cancer cells. PL, a small-molecule hydrophobic drug, was encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles. TRAIL was chemically conjugated to the surface of liposomes. PL was first administered to sensitize cancer cells to the effects of TRAIL. PC3 and HCT116 cells had lower survival rates in vitro after receiving the dual nanoparticle therapy compared to each agent individually. In vivo testing involved a subcutaneous mouse xenograft model using NOD-SCID gamma mice and HCT116 cells. Two treatment cycles were administered over 48 hours. Higher apoptotic rates were observed for HCT116 tumor cells that received the dual nanoparticle therapy compared to individual stages of the nanoparticle therapy alone.

A hypoxia-specific and mitochondria-targeted anticancer theranostic agent with high selectivity for cancer cells

2018 ◽  
Vol 6 (16) ◽  
pp. 2413-2416 ◽  
Author(s):  
Mingxing Hu ◽  
Chao Yang ◽  
Yi Luo ◽  
Fan Chen ◽  
Fangfang Yang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
High Selectivity ◽  
Theranostic Agent ◽  
Anti Cancer

A novel hypoxia-specific and mitochondria-targeted theranostic agent,HMX-1, was reported with certified anti-cancer efficiencyin vitroandin vivo.

Elemene displays anti-cancer ability on laryngeal cancer cells in vitro and in vivo

2005 ◽  
Vol 58 (1) ◽  
pp. 24-34 ◽  
Author(s):  
Lei Tao ◽  
Liang Zhou ◽  
Luying Zheng ◽  
Min Yao
Keyword(s):  
Cancer Cells ◽  
Laryngeal Cancer ◽  
Anti Cancer

scholarly journals Hydroquinone Exhibits In Vitro and In Vivo Anti-Cancer Activity in Cancer Cells and Mice

2018 ◽  
Vol 19 (3) ◽  
pp. 903 ◽  
Author(s):  
Se Byeon ◽  
Young-Su Yi ◽  
Jongsung Lee ◽  
Woo Yang ◽  
Ji Kim ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anti Cancer ◽  
Cancer Activity

scholarly journals Five-Decade Update on Chemopreventive and Other Pharmacological Potential of Kurarinone: a Natural Flavanone

2021 ◽  
Vol 12 ◽  
Author(s):  
Shashank Kumar ◽  
Kumari Sunita Prajapati ◽  
Mohd Shuaib ◽  
Prem Prakash Kushwaha ◽  
Hardeep Singh Tuli ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Therapeutic Potential ◽  
Experimental Models ◽  
Xenograft Models ◽  
Inhibitory Potential ◽  
Pharmacological Potential

In the present article we present an update on the role of chemoprevention and other pharmacological activities reported on kurarinone, a natural flavanone (from 1970 to 2021). To the best of our knowledge this is the first and exhaustive review of kurarinone. The literature was obtained from different search engine platforms including PubMed. Kurarinone possesses anticancer potential against cervical, lung (non-small and small), hepatic, esophageal, breast, gastric, cervical, and prostate cancer cells. In vivo anticancer potential of kurarinone has been extensively studied in lungs (non-small and small) using experimental xenograft models. In in vitro anticancer studies, kurarinone showed IC50 in the range of 2–62 µM while in vivo efficacy was studied in the range of 20–500 mg/kg body weight of the experimental organism. The phytochemical showed higher selectivity toward cancer cells in comparison to respective normal cells. kurarinone inhibits cell cycle progression in G2/M and Sub-G1 phase in a cancer-specific context. It induces apoptosis in cancer cells by modulating molecular players involved in apoptosis/anti-apoptotic processes such as NF-κB, caspase 3/8/9/12, Bcl2, Bcl-XL, etc. The phytochemical inhibits metastasis in cancer cells by modulating the protein expression of Vimentin, N-cadherin, E-cadherin, MMP2, MMP3, and MMP9. It produces a cytostatic effect by modulating p21, p27, Cyclin D1, and Cyclin A proteins in cancer cells. Kurarinone possesses stress-mediated anticancer activity and modulates STAT3 and Akt pathways. Besides, the literature showed that kurarinone possesses anti-inflammatory, anti-drug resistance, anti-microbial (fungal, yeast, bacteria, and Coronavirus), channel and transporter modulation, neuroprotection, and estrogenic activities as well as tyrosinase/diacylglycerol acyltransferase/glucosidase/aldose reductase/human carboxylesterases 2 inhibitory potential. Kurarinone also showed therapeutic potential in the clinical study. Further, we also discussed the isolation, bioavailability, metabolism, and toxicity of Kurarinone in experimental models.

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