A novel anticancer pharmacological agent targeting mitochondrial complex I

Reyes-Castellanos, Gabriela; Carrier, Alice

doi:10.1016/j.tips.2022.03.007

Cited by 3 publications

(2 citation statements)

References 10 publications

(32 reference statements)

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“…Thus, by inhibiting the metabolic pathways of tumor cells, the occurrence and development of tumors could be prevented. Therefore, targeting tumor metabolism is a promising therapeutic approach ( Wang et al, 2022b ; DeBerardinis and Keshari, 2022 ; Reyes-Castellanos and Carrier, 2022 ). Metabonomic results indicated that STA treatment decreased the production of D-glucose, lactate, L-alanine, L-proline, and serine.…”

Section: Discussionmentioning

confidence: 99%

Schisantherin A inhibits cell proliferation by regulating glucose metabolism pathway in hepatocellular carcinoma

Feng

Pan

et al. 2022

Front. Pharmacol.

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Schisantherin A (STA) is a traditional Chinese medicine extracted from the plant Schisandra chinensis, which has a wide range of anti-inflammatory, antioxidant, and other pharmacological effects. This study investigates the anti-hepatocellular carcinoma effects of STA and the underlying mechanisms. STA significantly inhibits the proliferation and migration of Hep3B and HCCLM3 cells in vitro in a concentration-dependent manner. RNA-sequencing showed that 77 genes are upregulated and 136 genes are downregulated in STA-treated cells compared with untreated cells. KEGG pathway analysis showed significant enrichment in galactose metabolism as well as in fructose and mannose metabolism. Further gas chromatography-mass spectrometric analysis (GC-MS) confirmed this, indicating that STA significantly inhibits the glucose metabolism pathway of Hep3B cells. Tumor xenograft in nude mice showed that STA has a significant inhibitory effect on tumor growth in vivo. In conclusion, our results indicate that STA can inhibit cell proliferation by regulating glucose metabolism, with subsequent anti-tumor effects, and has the potential to be a candidate drug for the treatment of liver cancer.

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Section: Discussionmentioning

confidence: 99%

Schisantherin A inhibits cell proliferation by regulating glucose metabolism pathway in hepatocellular carcinoma

Feng

Pan

et al. 2022

Front. Pharmacol.

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“…The first nuclear-encoded subunit mutations of complex I in a patient with Leigh syndrome are missense mutations in the NDUFS8, followed by several patients with different pathogenic variants [11]. In addition, with the development of the link between other subunits of complex I and cancer or diabetes mellitus, the results have gradually emerged, while the relation between NDUFS8 and these diseases is poorly studied [12][13][14][15]. Therefore, we summarize the structure, function, and possible roles or mechanisms of NDUFS8 in diseases in this review, establishing the foundation for future research.…”

Section: Introductionmentioning

confidence: 99%

Emerging Roles of NDUFS8 Located in Mitochondrial Complex I in Different Diseases

et al. 2022

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NADH:ubiquinone oxidoreductase core subunit S8 (NDUFS8) is an essential core subunit and component of the iron-sulfur (FeS) fragment of mitochondrial complex I directly involved in the electron transfer process and energy metabolism. Pathogenic variants of the NDUFS8 are relevant to infantile-onset and severe diseases, including Leigh syndrome, cancer, and diabetes mellitus. With over 1000 nuclear genes potentially causing a mitochondrial disorder, the current diagnostic approach requires targeted molecular analysis, guided by a combination of clinical and biochemical features. Currently, there are only several studies on pathogenic variants of the NDUFS8 in Leigh syndrome, and a lack of literature on its precise mechanism in cancer and diabetes mellitus exists. Therefore, NDUFS8-related diseases should be extensively explored and precisely diagnosed at the molecular level with the application of next-generation sequencing technologies. A more distinct comprehension will be needed to shed light on NDUFS8 and its related diseases for further research. In this review, a comprehensive summary of the current knowledge about NDUFS8 structural function, its pathogenic mutations in Leigh syndrome, as well as its underlying roles in cancer and diabetes mellitus is provided, offering potential pathogenesis, progress, and therapeutic target of different diseases. We also put forward some problems and solutions for the following investigations.

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Recent advances of mitochondrial complex I inhibitors for cancer therapy: Current status and future perspectives

Zhou

Zou

et al. 2023

European Journal of Medicinal Chemistry

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A novel anticancer pharmacological agent targeting mitochondrial complex I

Cited by 3 publications

References 10 publications

Schisantherin A inhibits cell proliferation by regulating glucose metabolism pathway in hepatocellular carcinoma

Schisantherin A inhibits cell proliferation by regulating glucose metabolism pathway in hepatocellular carcinoma

Emerging Roles of NDUFS8 Located in Mitochondrial Complex I in Different Diseases

Recent advances of mitochondrial complex I inhibitors for cancer therapy: Current status and future perspectives

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