Sirt3 promotes hepatocellular carcinoma cells sensitivity to regorafenib through the acceleration of mitochondrial dysfunction

Wang, Ruobing; Liu, Yahui; Mi, Xuguang; Chen, Qingmin; Jiang, Peiqiang; Hou, Junjie; Lin, Yifan; Li, Siqi; Bai, Jing; Yanqiu, Fang

doi:10.1016/j.abb.2020.108415

Cited by 8 publications

(3 citation statements)

References 46 publications

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“…SIRT3 deacetylase activity and mTOR have also been indicated in metabolic dysfunction in HCC patients, revealing that SIRT3 and HIF-1α are prognostic indicators in early-stage HCC patients [195]. Moreover, SIRT3 overexpression also promotes ROS and apoptosis induced by the HCC therapy regorafenib, a multiple kinase inhibitor and mitochondrial toxicant, by accelerating mitochondrial depolarization induced by regorafenib and inducing mitochondrial dysfunction through impaired ETC function [196]. Aside from mitochondrially directed deacetylase activity, SIRT6 depletion was found to downregulate multidrug resistance protein 1 (MDR1) expression through the suppression of CCAAT/enhancer-binding protein (C/EBPβ), promoting enhanced chemosensitivity to HCC [197].…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

Biochemical Mechanisms of Sirtuin-Directed Protein Acylation in Hepatic Pathologies of Mitochondrial Dysfunction

McGinnis

Jennings

Harris

et al. 2022

Cells

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Mitochondrial protein acetylation is associated with a host of diseases including cancer, Alzheimer’s, and metabolic syndrome. Deciphering the mechanisms regarding how protein acetylation contributes to disease pathologies remains difficult due to the complex diversity of pathways targeted by lysine acetylation. Specifically, protein acetylation is thought to direct feedback from metabolism, whereby nutritional status influences mitochondrial pathways including beta-oxidation, the citric acid cycle, and the electron transport chain. Acetylation provides a crucial connection between hepatic metabolism and mitochondrial function. Dysregulation of protein acetylation throughout the cell can alter mitochondrial function and is associated with numerous liver diseases, including non-alcoholic and alcoholic fatty liver disease, steatohepatitis, and hepatocellular carcinoma. This review introduces biochemical mechanisms of protein acetylation in the regulation of mitochondrial function and hepatic diseases and offers a viewpoint on the potential for targeted therapies.

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Section: Hepatocellular Carcinomamentioning

confidence: 99%

Biochemical Mechanisms of Sirtuin-Directed Protein Acylation in Hepatic Pathologies of Mitochondrial Dysfunction

McGinnis

Jennings

Harris

et al. 2022

Cells

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“…Recent studies have indicated that ROS regulates the progression, metastasis, DNA damage, and mitochondrial pathway in HCC [65,66]. Moreover, SIRT3 promotes the sensitivity of hepatocellular carcinoma cells to regorafenib by accelerating mitochondrial dysfunction [67,68]. Overall, the occurrence and development of HCC decrease the expression of SIRT3, thereby suggesting a new method to treat HCC.…”

Section: Sirt3mentioning

confidence: 99%

Epigenetics of Sirtuins: Relevance to Hepatocellular Carcinoma

Zhu¹,

Wang²,

Chang³

et al. 2021

Oncologie

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“…As an oral multikinase inhibitor, Regorafenib (REGO) provides antiangiogenic activity in various tumor types by the inhibition of vascular endothelial growth factor receptors (VEGFR), tyrosine kinase with immunoglobulin and epidermal growth factor homology domain 2 (TIE-2), platelet-derived growth factor receptor-β (PDGFR-β), and fibroblast growth factor receptor (FGFR) (Khan et al., 2020 ; Wang et al., 2020 ). The activity is correlated with suppression of cell proliferation, and induction of apoptosis by the inhibition of oncogenic kinases (KIT, RET, RAF-1, BRAF and mutant BRAF).…”

Section: Introductionmentioning

confidence: 99%

Co-drug delivery of regorafenib and cisplatin with amphiphilic copolymer nanoparticles: enhanced in vivo antitumor cancer therapy in nursing care

Zhou

2020

Drug Delivery

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Cancers continue to be the second leading cause of death worldwide. Despite the development and improvement of surgery, chemotherapy and radiotherapy in cancer management, effective tumor ablation strategies are still in need due to high cancer patient mortality. Hence, we have established a new approach to achieve treatment-actuated modifications in a tumor microenvironment by using synergistic activity between two potential anticancer drugs. Dual drug delivery of Regorafenib (REGO) and Cisplatin (PT) exhibits a great anticancer potential, as REGO enhances the effect of PT treatment of human cells by providing stability of the microenvironment. However, encapsulation of REGO and PT fanatical by methoxypoly(ethylene glycol)-block-poly(D, L-lactic acid) (PEG-PLA in termed as NPs) is incompetent owing to unsuitability between the binary Free REGO and PT core and the polymeric system. Now, we display that PT can be prepared by hydrophobic coating of the dual drug centers with dioleoylphosphatidic acid (DOPA). The DOPA-covered PT can be co-encapsulated in PLGA NPs alongside REGO to stimulate excellent anticancer property. The occurrence of the PT suggestively enhanced the encapsulations of REGO into PLGA NPs (REGO-PT NPs). Further, the morphology of REGO NPs, PT NPs, and REGO-PT NPs and nanoparticle size was examined by transmission microscopy (TEM), respectively. Furthermore REGO-PT NPs induced significant apoptosis in human lung A549 and ovarian A2780 cancer cells by in vitro. The morphological observation and apoptosis were confirmed by the various biochemical assayes (AO-EB, Nuclear Staining and Annexin V-FITC). In a xenograft model of lung cancer, this nanotherapy shows a durable inhibition of tumor progression upon the administration of a tolerable dose. Our results suggest that a hydrophobic and highly toxic drug can be rationally converted into a pharmacologically efficient and self-deliverable nursing care of nanotherapy. HIGHLIGHTS Dual drug delivery of Regorafenib (REGO) and Cisplatin (PT) exhibits a great anticancer potential, as REGO enhances the effect of PT treatment of human cells by providing stability of the microenvironment. REGO-PT NPs induced significant apoptosis in human lung A549 and ovarian A2780 cancer cells by in vitro. The morphological observation and apoptosis were confirmed by the various biochemical assayes. In a xenograft model of lung cancer, this nanotherapy shows a durable inhibition of tumor progression upon the administration of a tolerable dose.

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Sirt3 promotes hepatocellular carcinoma cells sensitivity to regorafenib through the acceleration of mitochondrial dysfunction

Cited by 8 publications

References 46 publications

Biochemical Mechanisms of Sirtuin-Directed Protein Acylation in Hepatic Pathologies of Mitochondrial Dysfunction

Biochemical Mechanisms of Sirtuin-Directed Protein Acylation in Hepatic Pathologies of Mitochondrial Dysfunction

Epigenetics of Sirtuins: Relevance to Hepatocellular Carcinoma

Co-drug delivery of regorafenib and cisplatin with amphiphilic copolymer nanoparticles: enhanced in vivo antitumor cancer therapy in nursing care

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