A new SIRT1 inhibitor, MHY2245, induces autophagy and inhibits energy metabolism via PKM2/mTOR pathway in human ovarian cancer cells

Tae, In; Son, Ji Yeon; Lee, Sang Ho; Ahn, Mi-Young; Yoon, Kyungsil; Yoon, Sungpil; Moon, Hyung Ryong; Kim, Hyung Sik

doi:10.7150/ijbs.44343

Cited by 31 publications

(23 citation statements)

References 63 publications

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“…apoptosis or autophagy (Carafa et al, 2018(Carafa et al, , 2019De et al, 2018;Tae et al, 2018Tae et al, , 2020Igase et al, 2020).…”

Section: Efficiency Of Hdacimentioning

confidence: 99%

“…HDACi can also induce DNA damage, cell cycle arrest, apoptosis and autophagy to promote cancer cell death mentioned above. Some novel SIRT inhibitors, such as MC2494, MHY2245, MHY2256, tenovin-6, and YC8-02, also perform diverse anti-tumor activities through mediating apoptosis or autophagy ( Carafa et al, 2018 , 2019 ; De et al, 2018 ; Tae et al, 2018 , 2020 ; Li M. et al, 2019 ; Igase et al, 2020 ).…”

Section: Hdac Inhibitors In Cancer Therapymentioning

confidence: 99%

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The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy

Guo

Tian

Zhu

2020

Front. Cell Dev. Biol.

180

135

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Genetic mutations and abnormal gene regulation are key mechanisms underlying tumorigenesis. Nucleosomes, which consist of DNA wrapped around histone cores, represent the basic units of chromatin. The fifth amino group (N ε) of histone lysine residues is a common site for post-translational modifications (PTMs), and of these, acetylation is the second most common. Histone acetylation is modulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), and is involved in the regulation of gene expression. Over the past two decades, numerous studies characterizing HDACs and HDAC inhibitors (HDACi) have provided novel and exciting insights concerning their underlying biological mechanisms and potential anti-cancer treatments. In this review, we detail the diverse structures of HDACs and their underlying biological functions, including transcriptional regulation, metabolism, angiogenesis, DNA damage response, cell cycle, apoptosis, protein degradation, immunity and other several physiological processes. We also highlight potential avenues to use HDACi as novel, precision cancer treatments.

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“…apoptosis or autophagy (Carafa et al, 2018(Carafa et al, , 2019De et al, 2018;Tae et al, 2018Tae et al, , 2020Igase et al, 2020).…”

Section: Efficiency Of Hdacimentioning

confidence: 99%

Section: Hdac Inhibitors In Cancer Therapymentioning

confidence: 99%

The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy

Guo

Tian

Zhu

2020

Front. Cell Dev. Biol.

180

135

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“…It is well known that autophagy plays a dual role in tumor development. It can serve as either a tumor suppressor to inhibit tumor progression or a cell survival enhancer to promote tumor growth [39,40]. On the one hand, autophagy recycles damaged cell components and provides substrates for biosynthesis and energy metabolism [39].…”

Section: Discussionmentioning

confidence: 99%

Rutin attenuates Sorafenib-induced Chemoresistance and Autophagy in Hepatocellular Carcinoma by regulating BANCR/miRNA-590-5P/OLR1 Axis

Zhou

Zhang

et al. 2021

Int. J. Biol. Sci.

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Rutin, the main component of Potentilla discolor Bunge, was proven to exhibit anti-tumor properties. Sorafenib (SO) is conventionally used in chemotherapy against hepatocellular carcinoma (HCC), but acquired resistance developed during long-term therapy limits its benefits. This study aimed to explore the molecular mechanism of rutin in SO-induced autophagy and chemoresistance in HCC. Sixty-eight paired HCC patients who received the same chemotherapy treatment were obtained. We also established two SO resistance cell lines and then utilized high-throughput RNA sequencing to explore their long non-coding RNA (lncRNA) expression profiles. The target microRNA (miRNA) and downstream mRNA were also explored. Our results indicated that rutin treatment attenuates autophagy and BANCR expression in SO resistance cells. Transmission electron microscopy clearly showed a significantly decreased number of autophagosomes after rutin-treated HepG2/SO and HCCLM3/SO cells. BANCR knockdown promotes the sensitivity of SO resistance cells to SO. Further study found that BANCR acts as a molecular sponge of miR-590-5P to sequester miR-590-5P away from oxidized low-density lipoprotein receptor 1 (OLR1) in HCC cells. Furthermore, in vivo study demonstrated that rutin could inhibit autophagy through the BANCR/miRNA-590-5P/OLR1 axis. Our findings suggest that rutin could regulate autophagy by regulating BANCR/miRNA-590-5P/OLR1 axis.

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“…PKM2’s role in aerobic glycolysis and cancer metabolism has been the focus of most of the literature and research to date [ 28 , 29 , 71 , 143 ]. Xenograft studies in mice injected with H1299 lung cancer cells overexpressing the mouse PKM1 or PKM2 isoforms then stably knocked down for the endogenous PKM2 revealed that PKM2 is necessary for aerobic glycolysis.…”

Section: “Metabolic” and “Non-metabolic” Functions Of Pkm2mentioning

confidence: 99%

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

Puckett

Alquraishi

Chowanadisai

et al. 2021

IJMS

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Pyruvate kinase is a key regulator in glycolysis through the conversion of phosphoenolpyruvate (PEP) into pyruvate. Pyruvate kinase exists in various isoforms that can exhibit diverse biological functions and outcomes. The pyruvate kinase isoenzyme type M2 (PKM2) controls cell progression and survival through the regulation of key signaling pathways. In cancer cells, the dimer form of PKM2 predominates and plays an integral role in cancer metabolism. This predominance of the inactive dimeric form promotes the accumulation of phosphometabolites, allowing cancer cells to engage in high levels of synthetic processing to enhance their proliferative capacity. PKM2 has been recognized for its role in regulating gene expression and transcription factors critical for health and disease. This role enables PKM2 to exert profound regulatory effects that promote cancer cell metabolism, proliferation, and migration. In addition to its role in cancer, PKM2 regulates aspects essential to cellular homeostasis in non-cancer tissues and, in some cases, promotes tissue-specific pathways in health and diseases. In pursuit of understanding the diverse tissue-specific roles of PKM2, investigations targeting tissues such as the kidney, liver, adipose, and pancreas have been conducted. Findings from these studies enhance our understanding of PKM2 functions in various diseases beyond cancer. Therefore, there is substantial interest in PKM2 modulation as a potential therapeutic target for the treatment of multiple conditions. Indeed, a vast plethora of research has focused on identifying therapeutic strategies for targeting PKM2. Recently, targeting PKM2 through its regulatory microRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) has gathered increasing interest. Thus, the goal of this review is to highlight recent advancements in PKM2 research, with a focus on PKM2 regulatory microRNAs and lncRNAs and their subsequent physiological significance.

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A new SIRT1 inhibitor, MHY2245, induces autophagy and inhibits energy metabolism via PKM2/mTOR pathway in human ovarian cancer cells

Cited by 31 publications

References 63 publications

The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy

The Roles of Histone Deacetylases and Their Inhibitors in Cancer Therapy

Rutin attenuates Sorafenib-induced Chemoresistance and Autophagy in Hepatocellular Carcinoma by regulating BANCR/miRNA-590-5P/OLR1 Axis

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

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