SIRT3-Mediated SOD2 and PGC-1α Contribute to Chemoresistance in Colorectal Cancer Cells

Paku, Masakatsu; Haraguchi, Naotsugu; Takeda, Mitsunobu; Fujino, Shiki; Ogino, Takayuki; Takahashi, Hidekazu; Miyoshi, Norikatsu; Uemura, Mamoru; Mizushima, Tsuneo; Yamamoto, Hirofumi; Doki, Yuichiro; Eguchi, Hidetoshi

doi:10.1245/s10434-020-09373-x

Cited by 34 publications

(27 citation statements)

References 36 publications

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“…Although the exact role of PGC-1α in cancer is not entirely understood, since it can be upregulated or downregulated in diverse cancer types [128], its role in chemoresistance has been reported. Paku et al demonstrated that sirtuin 3 (SIRT3) increased colorectal cancer cell chemoresistance through SOD2 and PGC-1α up-regulation, and SIRT3 inhibition sensitized cancer cells to the chemotherapy [129]. Cruz-Bermúdez et al reported that SCLC cells, with increased PGC-1a, induced by ZLN005 treatment, showed reduced cisplatin-driven apoptosis, whereas PGC-1α interference increased cisplatin sensitivity [130].…”

Section: Pgc-1a and Yap Transcriptional Coactivatorsmentioning

confidence: 99%

Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

et al. 2021

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Chemoresistance represents the main obstacle to cancer treatment with both conventional and targeted therapy. Beyond specific molecular alterations, which can lead to targeted therapy, metabolic remodeling, including the control of redox status, plays an important role in cancer cell survival following therapy. Although cancer cells generally have a high basal reactive oxygen species (ROS) level, which makes them more susceptible than normal cells to a further increase of ROS, chemoresistant cancer cells become highly adapted to intrinsic or drug-induced oxidative stress by upregulating their antioxidant systems. The antioxidant response is principally mediated by the transcription factor Nrf2, which has been considered the master regulator of antioxidant and cytoprotective genes. Nrf2 expression is often increased in several types of chemoresistant cancer cells, and its expression is mediated by diverse mechanisms. In addition to Nrf2, other transcription factors and transcriptional coactivators can participate to maintain the high antioxidant levels in chemo and radio-resistant cancer cells. The control of expression and function of these molecules has been recently deepened to identify which of these could be used as a new therapeutic target in the treatment of tumors resistant to conventional therapy. In this review, we report the more recent advances in the study of Nrf2 regulation in chemoresistant cancers and the role played by other transcription factors and transcriptional coactivators in the control of antioxidant responses in chemoresistant cancer cells.

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Section: Pgc-1a and Yap Transcriptional Coactivatorsmentioning

confidence: 99%

Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

et al. 2021

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“…Conversely, SIRT3 ability to decrease ROS levels interferes with oxaliplatin-induced apoptosis, decreasing the chemotherapy effect [ 113 ]. SIRT3 levels represent predictive factor of chemotherapeutic success increasing PGC1α and SOD2 expression, consequentially determining reduction in mitochondrial ROS (mtROS) and increased drug resistance ( Figure 2 ) [ 117 ]. Emerging prevention strategies to counteract the development of CRC also include nutrition interventions, given the ability of many nutrients to act as exert anticancer effects through the modulation of SIRTs.…”

Section: Mitochondrial Sirtuins and Crcmentioning

confidence: 99%

Mitochondrial Sirtuins in Chronic Degenerative Diseases: New Metabolic Targets in Colorectal Cancer

Colloca¹,

Balestrieri²,

Anastasio³

et al. 2022

IJMS

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Sirtuins (SIRTs) are a family of class III histone deacetylases (HDACs) consisting of seven members, widely expressed in mammals. SIRTs mainly participate in metabolic homeostasis, DNA damage repair, cell survival, and differentiation, as well as other cancer-related biological processes. Growing evidence shows that SIRTs have pivotal roles in chronic degenerative diseases, including colorectal cancer (CRC), the third most frequent malignant disease worldwide. Metabolic alterations are gaining attention in the context of CRC development and progression, with mitochondrion representing a crucial point of complex and intricate molecular mechanisms. Mitochondrial SIRTs, SIRT2, SIRT3, SIRT4 and SIRT5, control mitochondrial homeostasis and dynamics. Here, we provide a comprehensive review on the latest advances on the role of mitochondrial SIRTs in the initiation, promotion and progression of CRC. A deeper understanding of the pathways by which mitochondrial SIRTs control CRC metabolism may provide new molecular targets for future innovative strategies for CRC prevention and therapy.

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“…In addition, SIRT3 has been demonstrated to be an independent prognostic factor in colon cancer. SIRT3 facilitates chemoresistance in colon cancer cells by regulating SOD2 and PGC-1α ( Paku et al, 2021 ). Therefore, SIRT3 may be a therapeutic and novel target for inhibiting colon cancer.…”

Section: The Roles Of Sirtuin3 In Cancermentioning

confidence: 99%

The Double-Edged Sword of SIRT3 in Cancer and Its Therapeutic Applications

et al. 2022

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Reprogramming of cellular energy metabolism is considered an emerging feature of cancer. Mitochondrial metabolism plays a crucial role in cancer cell proliferation, survival, and metastasis. As a major mitochondrial NAD+-dependent deacetylase, sirtuin3 (SIRT3) deacetylates and regulates the enzymes involved in regulating mitochondrial energy metabolism, including fatty acid oxidation, the Krebs cycle, and the respiratory chain to maintain metabolic homeostasis. In this article, we review the multiple roles of SIRT3 in various cancers, and systematically summarize the recent advances in the discovery of its activators and inhibitors. The roles of SIRT3 vary in different cancers and have cell- and tumor-type specificity. SIRT3 plays a unique function by mediating interactions between mitochondria and intracellular signaling. The critical functions of SIRT3 have renewed interest in the development of small molecule modulators that regulate its activity. Delineation of the underlying mechanism of SIRT3 as a critical regulator of cell metabolism and further characterization of the mitochondrial substrates of SIRT3 will deepen our understanding of the role of SIRT3 in tumorigenesis and progression and may provide novel therapeutic strategies for cancer targeting SIRT3.

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SIRT3-Mediated SOD2 and PGC-1α Contribute to Chemoresistance in Colorectal Cancer Cells

Cited by 34 publications

References 36 publications

Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

Control of Oxidative Stress in Cancer Chemoresistance: Spotlight on Nrf2 Role

Mitochondrial Sirtuins in Chronic Degenerative Diseases: New Metabolic Targets in Colorectal Cancer

The Double-Edged Sword of SIRT3 in Cancer and Its Therapeutic Applications

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