Anticancer Effects of Honokiol via Mitochondrial Dysfunction Are Strongly Enhanced by the Mitochondria-Targeting Carrier Berberine

2020 ◽  
Vol 63 (20) ◽  
pp. 11786-11800
Author(s):  
Xiaojia Shi ◽  
Tao Zhang ◽  
Hongxiang Lou ◽  
Huina Song ◽  
Changhao Li ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Anticancer Effects ◽  
Mitochondria Targeting

scholarly journals Targeting Mitochondria as Therapeutic Strategy for Metabolic Disorders

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Daniela Sorriento ◽  
Antonietta Valeria Pascale ◽  
Rosa Finelli ◽  
Anna Lisa Carillo ◽  
Roberto Annunziata ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Mitochondrial Dysfunction ◽  
Small Molecules ◽  
Metabolic Disorders ◽  
Therapeutic Strategy ◽  
Cell Metabolism ◽  
Therapeutic Interventions ◽  
Mtdna Mutations ◽  
Pathological Conditions ◽  
Mitochondria Targeting

Mitochondria are critical regulator of cell metabolism; thus, mitochondrial dysfunction is associated with many metabolic disorders. Defects in oxidative phosphorylation, ROS production, or mtDNA mutations are the main causes of mitochondrial dysfunction in many pathological conditions such as IR/diabetes, metabolic syndrome, cardiovascular diseases, and cancer. Thus, targeting mitochondria has been proposed as therapeutic approach for these conditions, leading to the development of small molecules to be tested in the clinical scenario. Here we discuss therapeutic interventions to treat mitochondrial dysfunction associated with two major metabolic disorders, metabolic syndrome, and cancer. Finally, novel mechanisms of regulation of mitochondrial function are discussed, which open new scenarios for mitochondria targeting.

scholarly journals Cannabidiol promotes apoptosis via regulation of XIAP/Smac in gastric cancer

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Soyeon Jeong ◽  
Min Jee Jo ◽  
Hye Kyeong Yun ◽  
Dae Yeong Kim ◽  
Bo Ram Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Therapeutic Target ◽  
Cannabis Sativa ◽  
Protein Family ◽  
Protein Levels ◽  
Anticancer Effects ◽  
Main Components ◽  
Induced Apoptosis

Abstract According to recent studies, Cannabidiol (CBD), one of the main components of Cannabis sativa, has anticancer effects in several cancers. However, the exact mechanism of CBD action is not currently understood. Here, CBD promoted cell death in gastric cancer. We suggest that CBD induced apoptosis by suppressing X-linked inhibitor apoptosis (XIAP), a member of the IAP protein family. CBD reduced XIAP protein levels while increasing ubiquitination of XIAP. The expression of Smac, a known inhibitor of XIAP, was found to be elevated during CBD treatment. Moreover, CBD treatment increased the interaction between XIAP and Smac by increasing Smac release from mitochondria to the cytosol. CBD has also been shown to affect mitochondrial dysfunction. Taken together, these results suggest that CBD may have potential as a new therapeutic target in gastric cancer.

Antitumoral effects of mitochondria-targeting neutral and cationic cis-[bis(1,3-dibenzylimidazol-2-ylidene)Cl(L)]Pt(ii) complexes

2020 ◽  
Vol 49 (26) ◽  
pp. 8901-8910 ◽  
Author(s):  
Matthias Rothemund ◽  
Sofia I. Bär ◽  
Tobias Rehm ◽  
Hana Kostrhunova ◽  
Viktor Brabec ◽  
...  
Keyword(s):  
Anticancer Effects ◽  
Mitochondria Targeting

cis-[Bis(1,3-dibenzylimidazol-2-ylidene)PtIICl(L)] complexes target mitochondria regardless of charge and size of ligands L, yet show different anticancer effects.

Abstract P022: Evidence For A Physiological Mitochondrial Angiotensin Ii System In The Proximal Tubules Of The Kidney

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Xiao C Li ◽  
Xinchun Zhou ◽  
Jia L Zhuo
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Mitochondrial Dysfunction ◽  
Kidney Diseases ◽  
Physiological Role ◽  
Proximal Tubules ◽  
Ang Ii ◽  
New Evidence ◽  
Mitochondria Targeting

Angiotensin II (Ang II) has long been implicated in mediating mitochondrial dysfunction in cardiovascular, hypertension, and kidney diseases. However, whether it is circulating and paracrine Ang II or intracellular mitochondrial Ang II that induces mitochondrial dysfunction has not been studied previously. The present study tested the hypotheses that overexpression of an intracellular angiotensin II (Ang II) fusion protein, mito-ECFP/Ang II, selectively in the mitochondria of mouse proximal tubule (mPCT) cells induces mitochondrial oxidative and glycolytic responses and elevates blood pressure via the Ang II/AT 1a receptor/superoxide/NHE3 (the Na + /H + exchanger 3)-dependent mechanisms. A proximal tubule-selective, mitochondria-targeting adenoviral construct encoding Ad-sglt2-mito-ECFP/Ang II was used to test the hypotheses. The expression of mito-ECFP/Ang II was colocalized primarily with Mito-Tracker® Red FM in mPCT cells or with TMRM in kidney proximal tubules. mito-ECFP/Ang II markedly increased oxygen consumption rate (OCR) as an index of mitochondrial oxidative response (69.5%; P <0.01) and extracellular acidification rate (ECAR) as an index of mitochondrial glycolytic response (34%; P <0.01). The mito-ECFP/Ang II-induced OCR and ECAR responses were blocked by AT 1 blocker losartan ( P <0.01) and a mitochondria-targeting superoxide scavenger mito-TEMPO ( P <0.01). By contrast, the non-selective NO inhibitor L-NAME alone increased, whereas the mitochondria-targeting expression of AT 2 receptors (mito-AT 2 /GFP) attenuated the effects of mito-ECFP/Ang II ( P <0.01). In the kidney, overexpression of mito-ECFP/Ang II in the mitochondria of the proximal tubules increased systolic blood pressure 12 ± 3 mmHg ( P <0.01), and the response was attenuated in proximal tubule (PT)-specific PT- Agtr1a -/- and PT- Nhe3 -/- mice ( P <0.01). Conversely, overexpression of AT 2 receptors selectively in the mitochondria of the proximal tubules induced natriuretic responses in PT- Agtr1a -/- and PT- Nhe3 -/- mice ( P <0.01). Taken together, these results provide new evidence for a physiological role of proximal tubule mitochondrial Ang II/AT 1a /superoxide/NHE3 and Ang II/AT 2 /NO/NHE3 signaling pathways in maintaining blood pressure homeostasis.

Mitochondria-targeting cyclometalated iridium(iii) complexes for tumor hypoxic imaging and therapy

2019 ◽  
Vol 6 (4) ◽  
pp. 1003-1010 ◽  
Author(s):  
Jia Li ◽  
Hongmin Chen ◽  
Leli Zeng ◽  
Thomas W. Rees ◽  
Kai Xiong ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Cancer Cells ◽  
Hela Cells ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Turn On ◽  
Induce Cell Apoptosis ◽  
Theranostic Agents ◽  
Mitochondria Targeting

The organometallic anthraquinone iridium(iii) complexes display an efficient turn-on phosphorescence response to hypoxia. The complexes can induce cell apoptosis in HeLa cells via mitochondrial dysfunction and caspase-3 activation making them excellent candidates as theranostic agents for hypoxic cancer cells.

scholarly journals Anticancer Properties of Platinum Nanoparticles and Retinoic Acid: Combination Therapy for the Treatment of Human Neuroblastoma Cancer

2020 ◽  
Vol 21 (18) ◽  
pp. 6792
Author(s):  
Sangiliyandi Gurunathan ◽  
Muniyandi Jeyaraj ◽  
Min-Hee Kang ◽  
Jin-Hoi Kim
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Transcription Factor ◽  
Retinoic Acid ◽  
Mitochondrial Dysfunction ◽  
Platinum Nanoparticles ◽  
B Cell Lymphoma ◽  
Human Neuroblastoma ◽  
Anticancer Effects ◽  
Activating Transcription Factor

Neuroblastoma is the most common extracranial solid tumor in childhood. The different treatments available for neuroblastoma are challenged by high rates of resistance, recurrence, and progression, most notably in advanced cases and highly malignant tumors. Therefore, the development of more targeted therapies, which are biocompatible and without undesired side effects, is highly desirable. The mechanisms of actions of platinum nanoparticles (PtNPs) and retinoic acid (RA) in neuroblastoma have remained unclear. In this study, the anticancer effects of PtNPs and RA on neuroblastoma were assessed. We demonstrated that treatment of SH-SY5Y cells with the combination of PtNPs and RA resulted in improved anticancer effects. The anticancer effects of the two compounds were mediated by cytotoxicity, oxidative stress (OS), mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and apoptosis-associated networks. Cytotoxicity was confirmed by leakage of lactate dehydrogenase (LDH) and intracellular protease, and oxidative stress increased the level of reactive oxygen species (ROS), 4-hydroxynonenal (HNE), malondialdehyde (MDA), and nitric oxide (NO), and protein carbonyl content (PCC). The combination of PtNPs and RA caused mitochondrial dysfunction by decreasing the mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, number of mitochondria, and expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Endoplasmic reticulum-mediated stress and apoptosis were confirmed by upregulation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), activating transcription factor 4 (ATF4), p53, Bax, and caspase-3 and down regulation of B-cell lymphoma 2 (BCl-2). PtNPs and RA induced apoptosis, and oxidative DNA damage was evident by the accumulation of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG). Finally, PtNPs and RA increased the differentiation and expression of differentiation markers. Differentiated SH-SY5Y cells pre-treated with PtNPs or RA or the combination of both were more sensitive to the cytotoxic effect of cisplatin than undifferentiated cells. To our knowledge, this is the first study to demonstrate the effect of the combination of PtNPs and RA in neuroblastoma cells. PtNPs may be a potential preconditioning or adjuvant compound in chemotherapeutic treatment. The results of this study provide a rationale for clinical evaluation of the combination of PtNPs and RA for the treatment of children suffering from high-risk neuroblastoma.

scholarly journals Mitochondria targeting IR780-based nanoGUMBOS for enhanced selective toxicity towards cancer cells

RSC Advances ◽  
2018 ◽  
Vol 8 (55) ◽  
pp. 31700-31709 ◽  
Author(s):  
Mi Chen ◽  
Nimisha Bhattarai ◽  
Mingyan Cong ◽  
Rocío L. Pérez ◽  
Karen C. McDonough ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Self Assembly ◽  
Selective Toxicity ◽  
Anticancer Effects ◽  
Mitochondria Targeting

Mitochondria targeting nanoGUMBOS were successfully fabricated based on self-assembly of IR780 GUMBOS with different counter-anions that show promising anticancer effects.

scholarly journals Atherosclerosis as Mitochondriopathy: Repositioning the Disease to Help Finding New Therapies

2021 ◽  
Vol 8 ◽  
Author(s):  
Taisiia Shemiakova ◽  
Ekaterina Ivanova ◽  
Wei-Kai Wu ◽  
Tatiana V. Kirichenko ◽  
Antonina V. Starodubova ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Chronic Inflammation ◽  
Arterial Wall ◽  
Metabolic Dysfunction ◽  
Targeting Therapy ◽  
Mtdna Mutations ◽  
Human Disorders ◽  
Intracellular Lipid Accumulation ◽  
Abnormal Lipid Metabolism ◽  
Mitochondria Targeting

Atherosclerosis is a complex pathology that involves both metabolic dysfunction and chronic inflammatory process. During the last decade, a considerable progress was achieved in describing the pathophysiological features of atherosclerosis and developing approaches that target the abnormal lipid metabolism and chronic inflammation. However, early events in the arterial wall that initiate the disease development still remain obscure. Finding effective therapeutic targets in these early processes would allow developing methods for disease prevention and, possibly, atherosclerotic plaque regression. Currently, these early events are being actively studied by several research groups. One of the processes that are being investigated is the development of mitochondrial dysfunction, which was demonstrated to be present in the affected areas of the arterial wall. Detection and characterization of mitochondrial dysfunction associated with several chronic human disorders was made possible by the improved methods of studying mitochondrial biology and detecting mitochondrial DNA (mtDNA) mutations. It was found to be involved in several key atherogenic processes, such as oxidative stress, chronic inflammation, and intracellular lipid accumulation. Mitochondrial dysfunction can occur in all types of cells involved in the pathogenesis of atherosclerosis: monocytes and macrophages, smooth muscle cells, lymphocytes, and the endothelial cells. However, therapies that would specifically target the mitochondria to correct mitochondrial dysfunction and neutralize the defective organelles are still remain to be developed and characterized. The aim of this review is to outline the prospects for mitochondrial therapy for atherosclerosis. We discuss mechanisms of mitochondria-mediated atherogenic processes, known mitochondria-targeting therapy strategies, and novel mitochondria-targeting drugs in the context of atherosclerosis.

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