Knockdown of vps54 aggravates tamoxifen-induced cytotoxicity in fission yeast

Tamoxifen (TAM) is an anticancer drug used to treat estrogen receptor (ER)‒positive breast cancer. However, its ER-independent cytotoxic and antifungal activities have prompted debates on its mechanism of action. To achieve a better understanding of the ER-independent antifungal action mechanisms of TAM, we systematically identified TAM-sensitive genes through microarray screening of the heterozygous gene deletion library in fission yeast (Schizosaccharomyces pombe). Secondary confirmation was followed by a spotting assay, finally yielding 13 TAM-sensitive genes under the drug-induced haploinsufficient condition. For these 13 TAM-sensitive genes, we conducted a comparative analysis of their Gene Ontology (GO) ‘biological process’ terms identified from other genome-wide screenings of the budding yeast deletion library and the MCF7breast cancer cell line. Several TAM-sensitive genes overlapped between the yeast strains and MCF7 in GO terms including ‘cell cycle’ (cdc2, rik1, pas1, and leo1), ‘signaling’ (sck2, oga1, and cki3), and ‘vesicle-mediated transport’ (SPCC126.08c, vps54, sec72, and tvp15), suggesting their roles in the ER-independent cytotoxic effects of TAM. We recently reported that the cki3 gene with the ‘signaling’ GO term was related to the ER-independent antifungal action mechanisms of TAM in yeast. In this study, we report that haploinsufficiency of the essential vps54 gene, which encodes the GARP complex subunit, significantly aggravated TAM sensitivity and led to an enlarged vesicle structure in comparison with the SP286 control strain. These results strongly suggest that the vesicle-mediated transport process might be another action mechanism of the ER-independent antifungal or cytotoxic effects of TAM.

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Cytotoxic Effect of 5-Fluorouracil-loaded Polymer-coated Magnetite Nanographene Oxide Combined with Radiofrequency

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180404151218 ◽

2018 ◽

Vol 18 (8) ◽

pp. 1148-1155 ◽

Cited By ~ 6

Author(s):

Leili Asadi ◽

Sakine Shirvalilou ◽

Sepideh Khoee ◽

Samideh Khoei

Keyword(s):

Cellular Uptake ◽

Cancer Cell Line ◽

Superparamagnetic Iron Oxide ◽

Colon Cancer Cell Line ◽

Cytotoxic Effects ◽

Proliferation Capacity ◽

Capacity Level ◽

Colony Number ◽

Nano Graphene ◽

Dialysis Bag

Background: Despite the development of conventional therapies including surgery, radiotherapy, chemotherapy and hyperthermia, the prognosis remains very poor. Recently, integration of conventional therapy and multifunctional nanoparticles have attracted a lot of attention because it produces a synergistic effect and better diagnostic and therapeutic efficiency. Objective: This study aimed to investigate the uptake and cytotoxic effects of Polycaprolactone (PCL)/chitosan (CHI)-coated Superparamagnetic Iron Oxide Nano-Graphene Oxide (SPION-NGO) as a carrier of 5-fluorouracil (5-Fu) and Radiofrequency (RF) hyperthermia using an Alternate Magnetic Field (AMF) with 13.56 MHz frequency on the proliferation capacity level of CT26 colon cancer cell line in a monolayer culture. Method: The release of the newly synthesised 5-Fu-loaded PCL/CHI-SPION-NGO was measured in Phosphate Buffered Saline (PBS) using the dialysis bag method. The cellular uptake of 5-Fu-loaded PCL/CHI-SPIONNGO was measured using Atomic Absorption Spectroscopy (AAS). The cytotoxic effects of 5-Fu, 5-Fu- PCL/CHI-SPION-NGO and PCL/CHI-SPION-NGO with and without RF hyperthermia were determined using the colony formation assay. Results: Particle size and zeta potential of 5-Fu-PCL/CHI-SPION-NGO and PCL/CHI-SPION-NGO were 61.2 nm and -1.87 mV and 43.4 nm and -10.19 mV, respectively. Spectroscopy results demonstrated that the cellular uptake of 5-Fu-PCL/CHI-SPION-NGO increased with elevated nanostructure concentrations. The results revealed that the proliferation capacity of the cells decreased with 5-Fu or 5-Fu-PCL/CHI-SPION-NGO in combination with RF hyperthermia. Furthermore, extent of reduction in colony number following treatment with 5-Fu-PCL/CHI-SPION-NGO in combination with AMF was significantly more than 5-Fu + hyperthermia. Conclusion: Therefore, PCL/CHI-SPION-NGO can deliver 5-Fu more efficiently into the CT26 cells.

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Adapting and Surviving: Intra and Extra-Cellular Remodeling in Drug-Resistant Gastric Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms20153736 ◽

2019 ◽

Vol 20 (15) ◽

pp. 3736 ◽

Cited By ~ 12

Author(s):

Sabino Russi ◽

Henu Kumar Verma ◽

Simona Laurino ◽

Pellegrino Mazzone ◽

Giovanni Storto ◽

...

Keyword(s):

Gastric Cancer ◽

Drug Resistance ◽

Epithelial Mesenchymal Transition ◽

Current Approach ◽

Gastric Cancer Cells ◽

Drug Induced ◽

Cytotoxic Effects ◽

Mesenchymal Transition ◽

Damage Response ◽

Drug Detoxification

Despite the significant recent advances in clinical practice, gastric cancer (GC) represents a leading cause of cancer-related deaths in the world. In fact, occurrence of chemo-resistance still remains a daunting hindrance to effectiveness of the current approach to GC therapy. There is accumulating evidence that a plethora of cellular and molecular factors is implicated in drug-induced phenotypical switching of GC cells. Among them, epithelial-mesenchymal transition (EMT), autophagy, drug detoxification, DNA damage response and drug target alterations, have been reported as major determinants. Intriguingly, resistant GC phenotype may be the result of GC cell-induced tumor microenvironment (TME) remodeling, which is currently emerging as a key player in promoting drug resistance and overcoming cytotoxic effects of drugs. In this review, we discuss the possible mechanisms of drug resistance and their involvement in determining current GC therapies failure.

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FOXA1 overexpression mediates endocrine resistance by altering the ER transcriptome and IL-8 expression in ER-positive breast cancer

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1612835113 ◽

2016 ◽

Vol 113 (43) ◽

pp. E6600-E6609 ◽

Cited By ~ 61

Author(s):

Xiaoyong Fu ◽

Rinath Jeselsohn ◽

Resel Pereira ◽

Emporia F. Hollingsworth ◽

Chad J. Creighton ◽

...

Keyword(s):

Breast Cancer ◽

Endocrine Resistance ◽

Cancer Cell Line ◽

Estrogen Receptor Α ◽

Resistant Cell ◽

Transcriptional Reprogramming ◽

Er Positive ◽

Integrated Omics ◽

And Function

Forkhead box protein A1 (FOXA1) is a pioneer factor of estrogen receptor α (ER)–chromatin binding and function, yet its aberration in endocrine-resistant (Endo-R) breast cancer is unknown. Here, we report preclinical evidence for a role of FOXA1 in Endo-R breast cancer as well as evidence for its clinical significance. FOXA1 is gene-amplified and/or overexpressed in Endo-R derivatives of several breast cancer cell line models. Induced FOXA1 triggers oncogenic gene signatures and proteomic profiles highly associated with endocrine resistance. Integrated omics data reveal IL8 as one of the most perturbed genes regulated by FOXA1 and ER transcriptional reprogramming in Endo-R cells. IL-8 knockdown inhibits tamoxifen-resistant cell growth and invasion and partially attenuates the effect of overexpressed FOXA1. Our study highlights a role of FOXA1 via IL-8 signaling as a potential therapeutic target in FOXA1-overexpressing ER-positive tumors.

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Abietane diterpenes induce cytotoxic effects in human pancreatic cancer cell line MIA PaCa-2 through different modes of action

Phytochemistry ◽

10.1016/j.phytochem.2012.02.015 ◽

2012 ◽

Vol 78 ◽

pp. 107-119 ◽

Cited By ~ 40

Author(s):

Marcio Fronza ◽

Evelyn Lamy ◽

Stefan Günther ◽

Berta Heinzmann ◽

Stefan Laufer ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Line ◽

Cancer Cell ◽

Pancreatic Cancer Cell ◽

Pancreatic Cancer Cell Line ◽

Cancer Cell Line ◽

Human Pancreatic Cancer ◽

Human Pancreatic Cancer Cell ◽

Cytotoxic Effects ◽

Abietane Diterpenes

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Cytotoxic effects and apoptosis of solo black garlic (Allium sativum L.) extract on T47D breast cancer cell line

10.1063/5.0015736 ◽

2020 ◽

Author(s):

Endah Permatasari ◽

Farida ◽

Slamet Widiyanto

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cell Line ◽

Allium Sativum ◽

Cancer Cell Line ◽

Cytotoxic Effects ◽

T47d Breast Cancer Cell

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Grade 3 Hepatotoxicity following Fulvestrant, Palbociclib, and Erdafitinib Therapy in a Patient with ER-Positive/PR-Negative/HER2-Negative Metastatic Breast Cancer: A Case Report

Case Reports in Oncology ◽

10.1159/000506442 ◽

2020 ◽

Vol 13 (1) ◽

pp. 304-308 ◽

Cited By ~ 3

Author(s):

Alyssa Schlotman ◽

Adam Stater ◽

Kyle Schuler ◽

Judd Heideman ◽

Vandana Abramson

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Case Report ◽

Metastatic Breast ◽

Drug Induced ◽

Drug Induced Liver Injury ◽

Hepatotoxic Effect ◽

Er Positive ◽

Grade 3 ◽

Experienced Grade

A 49-year-old woman with ER-positive/PR-negative/HER2-negative metastatic breast cancer experienced Grade 3 hepatotoxicity following initiation of a clinical trial of fulvestrant, palbociclib, and erdafitinib. Fulvestrant was determined to be the drug most likely responsible for this hepatotoxic effect. This case report details the timing and nature of this drug-induced liver injury, adding support to an area that has yet to be described adequately in the existing literature.

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