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Acetalax (Oxyphenisatin acetate, NSC 59687) and Bisacodyl Cause Oncosis in Triple Negative Breast Cancer by Poisoning the Ion Exchange Membrane Protein TRPM4

ABSTRACT: Acetalax (Oxyphenisatin acetate, NSC 59687) and Bisacodyl Cause Oncosis in Triple Negative Breast Cancer by Poisoning the Ion Exchange Membrane Protein TRPM4

PROVIDER: PRJNA1118761 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29249906_1.fastq.gz	Fastqsanger.gz
	SRR29249906_2.fastq.gz	Fastqsanger.gz
	SRR29249907_1.fastq.gz	Fastqsanger.gz
	SRR29249907_2.fastq.gz	Fastqsanger.gz
	SRR29249908_1.fastq.gz	Fastqsanger.gz

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Acetalax (Oxyphenisatin acetate, NSC 59687) and Bisacodyl Cause Oncosis in Triple Negative Breast Cancer by Poisoning the Ion Exchange Membrane Protein TRPM4

Project description:Triple negative breast cancer (TNBC) is generally unresponsive to current therapies, and the development of new anticancer agents is needed. Oxyphenisatin acetate, called Acetalax, which was used as a laxative in the 1950’s, has recently been reported to have anticancer activity in murine models. In this study we demonstrate that Acetalax and its diphenolic laxative structural analog bisacodyl (Dulcolax) exhibit potent antiproliferative activity in TNBC cell lines. We show that both cause oncosis, a non-apoptotic cell death characterized by cellular and nuclear swelling and cell membrane blebbing that leads to mitochondrial dysfunction and ATP depletion. Acetalax was further shown to enhance immune and inflammatory responses and inhibit protein synthesis. Mechanistically, we provide evidence that TRPM4 (Transient Receptor Potential Melastatin member 4) is poisoned by Acetalax and bisacodyl. By blocking TRPM4, a monovalent cation channel, Acetalax and Bisacodyl cause oncosis, and TNBC cells without endogenous TRPM4 expression as well as TRPM 4 knockout TNBC cells were found to be Acetalax- and Bisacodyl resistant. TRPM4 was also lost in cells with acquired Acetalax resistance. Moreover TRPM4 is rapidly degraded by the ubiquitin-proteasome system upon acute exposure to Acetalax and bisacodyl. Together, these results demonstrate that TRPM4 is a previously unknown target of Acetalax and Bisacodyl and that TRPM4 expression in cancer cells is a predictor of Acetalax and Bisacodyl efficacy, and could be used for the clinical development of these drugs as anticancer agents.

2024-09-12 | GSE268793 | GEO

Acetalax (Oxyphenisatin Acetate, NSC 59687) and Bisacodyl Cause Oncosis in Triple-Negative Breast Cancer Cell Lines by Poisoning the Ion Exchange Membrane Protein TRPM4.

Project description:Triple-negative breast cancer (TNBC) is clinically aggressive and relatively unresponsive to current therapies. Therefore, the development of new anticancer agents is needed to satisfy clinical needs. Oxyphenisatin acetate (Acetalax), which had been used as a laxative, has recently been reported to have anticancer activity in murine models. In this study, we demonstrate that Acetalax and its diphenolic laxative structural analogue bisacodyl (Dulcolax) exhibit potent antiproliferative activity in TNBC cell lines and cause oncosis, a nonapoptotic cell death characterized by cellular and nuclear swelling and cell membrane blebbing, leading to mitochondrial dysfunction, ATP depletion, and enhanced immune and inflammatory responses. Mechanistically, we provide evidence that transient receptor potential melastatin member 4 (TRPM4) is poisoned by Acetalax and bisacodyl in MDA-MB468, BT549, and HS578T TNBC cells. MDA-MB231 and MDA-MB436 TNBC cells without endogenous TRPM4 expression as well as TRPM4-knockout TNBC cells were found to be Acetalax- and bisacodyl-resistant. Conversely, ectopic expression of TRPM4 sensitized MDA-MB231 and MDA-MB436 cells to Acetalax. TRPM4 was also lost in cells with acquired Acetalax resistance. Moreover, TRPM4 is rapidly degraded by the ubiquitin-proteasome system upon acute exposure to Acetalax and bisacodyl. Together, these results demonstrate that TRPM4 is a previously unknown target of Acetalax and bisacodyl and that TRPM4 expression in cancer cells is a predictor of Acetalax and bisacodyl efficacy and could be used for the clinical development of these drugs as anticancer agents.SignificanceAcetalax and bisacodyl kill cancer cells by causing oncosis following poisoning of the plasma membrane sodium transporter TRPM4 and represent a new therapeutic approach for TNBC.

| S-EPMC11322923 | biostudies-literature

Microarray analysis of MCF7 cells treated with NSC 59687 (Oxyphenisatin Acetate)

2013-03-13 | GSE45046 | GEO

Microarray analysis of MCF7 cells treated with NSC 59687 (Oxyphenisatin Acetate)

Project description:NSC 59687 (oxyphenisatin acetate) is a novel anti-cancer agent with selectivity for breast and ovarian cell lines To elucidate the transcripts differentially regulated following treatment with Oxyphenisatin acetate (NSC 59687) MCF7 cells were treated with 10 microM NSC 59687 for 24 hours followed by RNA extraction, cDNA synthesis and microarray analysis using Affymetrix huU133 plus 2.0 arrays

2013-03-13 | E-GEOD-45046 | biostudies-arrayexpress

Lectin microarray analysis of murine CTL EVs separated by ion exchange method

Project description:Lectin microarray analysis of murine CTL EVs separated by ion exchange method

| PRJNA612028 | ENA

miRNA microarray analysis of murine CTL EVs separated by ion exchange method [miRNA]

Project description:miRNA microarray analysis of murine CTL EVs separated by ion exchange method [miRNA]

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mRNA microarray analysis of murine CTL EVs separated by ion exchange method [mRNA]

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NSC-derived exosomes enhance therapeutic effects of NSC transplantation on cerebral ischemia in mice

Project description:Transplantation of neural stem cells (NSCs) has been proved to promote functional rehabilitation of brain lesions including ischemic stroke. However, the therapeutic effects of NSC transplantation is limited by the low survival and differentiation rates of NSCs due to the harsh environment in the brain after ischemic stroke. Here, we employed NSCs derived from human induced pluripotent stem cells (iPSCs) together with exosomes extracted from NSCs to treat cerebral ischemia induced by middle cerebral artery occlusion/reperfusion (MCAO/R) in mice. The results showed that NSC-derived exosomes significantly reduced the inflammatory response, alleviated oxidative stress after NSC transplantation, and facilitated NSCs differentiation in vivo. The combination of NSCs with exosomes ameliorated the injury of brain tissue including cerebral infarct, neuronal death and glial scarring, and promoted the motor function recovery. To explore the underlying mechanisms, we analyzed the miRNA profiles of NSC-derived exosomes and the potential downstream genes. Our study provided the rationale for the clinical application of NSC-derived exosomes as a supportive adjuvant for NSC transplantation after stroke.

2023-04-26 | GSE217074 | GEO

Regulators of histone exchange

Project description:Regulators of histone exchange

| PRJNA927495 | ENA

Dupond: Transcriptional analysis of a clinical case of acute dioxin poisoning.

Project description:Transcriptional analysis of a clinical case of acute dioxin poisoning. Tissue sampling : patient 5 months and patient 11 months : skin biopsieson the face under general anaesthesia; controls 1-4 : retroauricular skin biopsies under local anaesthesia

2012-03-30 | E-MTAB-617 | biostudies-arrayexpress

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