Compound Prunetin Induces Cell Death in Gastric Cancer Cell with Potent Anti-Proliferative Properties: In Vitro Assay, Molecular Docking, Dynamics, and ADMET Studies

Vetrivel, Preethi; Kim, Sang Woo; Ha, Sang Eun; Kim, Hun Hwan; Bhosale, Pritam Bhagwan; Senthil, Kalaiselvi

doi:10.3390/biom10071086

Cited by 35 publications

(28 citation statements)

References 53 publications

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“…Then, we investigated whether the miR-375/SLC7A11 axis regulates the stemness of GC cells through triggering ferroptosis. Considering that miR-375/SLC7A11 axis may play a role through other forms of cell death instead of inducing ferroptosis, GC cells with miR-375 overexpression or SLC7A11 knockdown were treated with Fer-1 (10 μM), apoptosis inhibitor Z-VAD-FMK (20 μM) [53], or necrosis inhibitor Nec-1 (0.1 mM) [54,55], and following by examining the stemness of GC cells. As shown in Fig.…”

Section: Mir-375 Attenuates the Stemness Of Gc Cells Mainly Through Triggering Ferroptosismentioning

confidence: 99%

MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis

et al. 2021

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Background Gastric cancer stem cells (CSCs) are the main causes of metastasis and drug resistance. We previously indicated that miR-375 can inhibit Helicobacter pylori-induced gastric carcinogenesis; here, we aim to explore the effects and mechanisms of miR-375 on gastric cancer (GC) cell stemness. Methods Lentivirus infection was used to construct GC cells with ectopic expression of miR-375. In vitro and in vivo experiments, including analysis of tumor spheroid formation, CD44+ sub-population with stemness, stemness marker expression, and tumor-initiating ability, were performed to evaluate the effects of miR-375 on the stemness of GC cells. Furthermore, microarray and bioinformatics analysis were performed to search the potential targets of miR-375 in GC cells. Luciferase reporter, RNA immunoprecipitation, and RNA-FISH assays were carried out to verify the targeting of miR-375. Subsequently, combined with tissue microarray analysis, erastin-resistant GC cells, transmission electron microscopy, a series of agonists and oxidative stress markers, the underlying mechanisms contributing to miR-375-mediated effects were explored. Results MiR-375 reduced the stemness of GC cells in vitro and in vivo. Mechanistically, SLC7A11 was identified as a direct target of miR-375 and miR-375 attenuated the stemness of GC cells mainly through triggering SLC7A11-dependent ferroptosis. Conclusion MiR-375 can trigger the ferroptosis through targeting SLC7A11, which is essential for miR-375-mediated inhibition on GC cell stemness. These results suggest that the miR-375/SLC7A11 regulatory axis could serve as a potential target to provoke the ferroptosis and thus attenuate the stemness of GC cells.

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Section: Mir-375 Attenuates the Stemness Of Gc Cells Mainly Through Triggering Ferroptosismentioning

confidence: 99%

MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis

et al. 2021

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“…Furthermore, RIP3 knockdown, apoptosis inhibitor (Z-VAD-fmk) or necrostatin-1 (Nec-1), the first well-established necroptosis inhibitor that exclusively suppressed RIP1 activity [50], all can in part rescue celastrol-induced GC cell death. Vetrivel et al [51] also came up with similar results through in vitro, vivo experiments, and silico molecular docking and simulation studies. They found that prunetin induced necroptosis-mediated human AGS cell death via activating the RIP3, leading to the phosphorylation of MLKL.…”

Section: Rips and Gastric Cancermentioning

confidence: 67%

Receptor-interacting protein in malignant digestive neoplasms

Zhang

et al. 2021

J. Cancer

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A deep and comprehensive understanding of factors that contribute to cancer initiation, progression, and evolution is of essential importance. Among them, the serine/threonine and tyrosine kinase-like kinases, also known as receptor interacting proteins (RIPs) or receptor interacting protein kinases (RIPKs), is emerging as important tumor-related proteins due to its complex regulation of cell survival, apoptosis, and necrosis. In this review, we mainly review the relevance of RIP to various malignant digestive neoplasms, including esophageal cancer, gastric cancer, colorectal cancer, hepatocellular carcinoma, gallbladder cancer, cholangiocarcinoma, and pancreatic cancer. Consecutive research on RIPs and its relationship with malignant digestive neoplasms is required, as it ultimately conduces to the etiology and treatment of cancer.

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“…The activated form of caspase 3 tends to cleave several DNA-dependent protein kinases and poly ADP ribose polymerase (PARP) [ 24 ]. The cleaved form of the protein PARP is recognized as an important apoptotic marker that aids in bringing cellular damage through DNA cleavage and induces apoptotic cell death [ 25 ]. Results obtained from western blot revealed that the apoptotic marker proteins cleaved PARP and cleaved caspase 3 showed significant increased expression in AGS cells upon treatment with PG, as shown in Figure 8 c. These data confirm that PG induces apoptotic cell death in AGS cells.…”

Section: Resultsmentioning

confidence: 99%

A Network Pharmacological Approach to Reveal the Pharmacological Targets and Its Associated Biological Mechanisms of Prunetin-5-O-Glucoside against Gastric Cancer

Vetrivel

Murugesan

Bhosale

et al. 2021

Cancers

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Gastric cancer (GC) is an aggressive malignancy with increased mortality rate and low treatment options. Increasing evidence suggests that network pharmacology will be a novel method for identifying the systemic mechanism of therapeutic compounds in diseases like cancer. The current study aimed to use a network pharmacology approach to establish the predictive targets of prunetin-5-O-glucoside (PG) against gastric cancer and elucidate its biological mechanisms. Primarily, genes associated with the pathogenesis of GC was identified from the DiGeNET database and targets of PG was obtained from the Swiss target prediction database. In total, 65 correlative hits were identified as anti-gastric cancer targets of PG. Functional enrichment and pathway analysis revealed significant biological mechanisms of the targets. Interaction of protein network and cluster analysis using STRING resulted in three crucial interacting hub targets namely, HSP90AA1, CDK2, and MMP1. Additionally, the in vitro cytotoxic potential of PG was assessed on three gastric cancer cells (AGS, MKN-28, and SNU-484). Furthermore, the crucial targets were validated using molecular docking, followed by their expressions being evaluated by western blot and Human Protein Atlas. The findings indicate that the pharmacological action of PG against GC might be associated with the regulation of three core targets: HSP90AA1, CDK2, and MMP1. Thus, the network pharmacology undertaken in the current study established the core active targets of PG, which may be extensively applied with further validations for treatment in GC.

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Compound Prunetin Induces Cell Death in Gastric Cancer Cell with Potent Anti-Proliferative Properties: In Vitro Assay, Molecular Docking, Dynamics, and ADMET Studies

Cited by 35 publications

References 53 publications

MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis

MiR-375 reduces the stemness of gastric cancer cells through triggering ferroptosis

Receptor-interacting protein in malignant digestive neoplasms

A Network Pharmacological Approach to Reveal the Pharmacological Targets and Its Associated Biological Mechanisms of Prunetin-5-O-Glucoside against Gastric Cancer

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