Targeting mitochondrial dysfunctions in pancreatic cancer evokes new therapeutic opportunities

Sarwar, Ammar; Zhu, Man; Su, Qi; Zhu, Zeren; Yang, Tianfeng; Chen, Yanbin; Peng, Xiujuan; Zhang, Yanmin

doi:10.1016/j.critrevonc.2022.103858

Cited by 8 publications

(10 citation statements)

References 135 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mitochondria serve as an important bioenergy hub to regulate the ATP production, ROS generation and apoptotic induction. 36 In this study, the generation of ROS was increased in Molt4 cells after 13-AC treatment.…”

Section: Discussionmentioning

confidence: 54%

“…It is worth to note that Hsp 90 inhibitors competed at ATP‐binding site with inhibition of the ATPase activity and ATP‐ADP exchange to induce the degradation of clients via the proteasome mechanism and recruited the ligation of ubiquitin and Hsp90. Mitochondria serve as an important bioenergy hub to regulate the ATP production, ROS generation and apoptotic induction 36 . In this study, the generation of ROS was increased in Molt4 cells after 13‐AC treatment.…”

Section: Discussionmentioning

confidence: 63%

See 1 more Smart Citation

Exploration of anti‐leukemic effect of soft coral‐derived 13‐acetoxysarcocrassolide: Induction of apoptosis via oxidative stress as a potent inhibitor of heat shock protein 90 and topoisomerase II

Chin

Hsu

et al. 2023

The Kaohsiung J of Med Scie

View full text Add to dashboard Cite

13‐Acetoxysarcocrassolide (13‐AC) is a marine cembranoid derived from the aquaculture soft coral of Lobophytum crassum. The cytotoxic effect of 13‐AC against leukemia cells was previously reported but its mechanism of action is still unexplored. In the current study, we showed that 13‐AC induced apoptosis of human acute lymphoblastic leukemia Molt4 cells, as evidenced by the cleavage of PARP and caspases, phosphatidylserine externalization, as well as the disruption of mitochondrial membrane potential. The use of N‐acetylcysteine (NAC), a reactive oxygen species (ROS) scavenger, attenuated the cytotoxic effect induced by 13‐AC. Molecular docking and thermal shift assay indicated that the cytotoxic mechanism of action of 13‐AC involved the inhibition of heat shock protein 90 (Hsp 90) activity by eliciting the level of Hsp 70 and topoisomerase IIα in Molt4 cells. 13‐AC also exhibited potent antitumor activity by reducing the tumor volume (48.3%) and weight (72.5%) in the in vivo Molt4 xenograft mice model. Our findings suggested that the marine cembranoid, 13‐AC, acted as a dual inhibitor of Hsp 90 and topoisomerase IIα, exerting more potent apoptotic activity via the enhancement of ROS generation.

show abstract

Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 63%

Exploration of anti‐leukemic effect of soft coral‐derived 13‐acetoxysarcocrassolide: Induction of apoptosis via oxidative stress as a potent inhibitor of heat shock protein 90 and topoisomerase II

Chin

Hsu

et al. 2023

The Kaohsiung J of Med Scie

View full text Add to dashboard Cite

show abstract

“…Currently, it has been known that energy imbalance was linked to neurological disorders, cancers, and metabolic diseases. The destruction of organelle integrity leads to the imbalance of intracellular environment and the barrier of information transmission between cells [ 28 ]. Gap junctions, a form of intercellular connections, have been implicated in the pathogenesis of diabetes and its complications.…”

Section: Discussionmentioning

confidence: 99%

Cartilage Damage Pathological Characteristics of Diabetic Neuropathic Osteoarthropathy

Liu

Diao

Wang

et al. 2023

Analytical Cellular Pathology

View full text Add to dashboard Cite

Background. Diabetic neuropathic osteoarthropathy (DNOAP) is a rare and easily missed complication for diabetes that leads to increased morbidity and mortality. DNOAP is characterized by progressive destruction of bone and joint, but its pathogenesis remains elusive. We herein aimed to investigate the pathological features and pathogenesis of the cartilages damage in DNOAP patients. Methods. The articular cartilages of eight patients with DNOAP and eight normal controls were included. Masson staining and safranine O/fixed green staining (S-O) were used to observe the histopathological characteristics of cartilage. The ultrastructure and morphology of chondrocytes were detected by electron microscopy and toluidine blue staining. Chondrocytes were isolated from DNOAP group and control group. The expression of receptor activator of nuclear factor kappaB ligand (RANKL), osteoprotegerin (OPG), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and Aggrecan protein was evaluated by western blot. Reactive oxygen species (ROS) levels were measured using a 2′,7′-dichlorofluorescin diacetate (DCFH-DA) probe. The percentage of apoptotic cells was determined by flow cytometry (FCM). The chondrocytes were cultured with different glucose concentrations to observe the expression of RANKL and OPG. Results. Compared with the control group, the DNOAP group showed fewer chondrocytes, subchondral bone hyperplasia, and structural disorder, and a large number of osteoclasts formed in the subchondral bone area. Moreover, mitochondrial and endoplasmic reticulum swellings were observed in the DNOAP chondrocytes. The chromatin was partially broken and concentrated at the edge of nuclear membrane. The ROS fluorescence intensity of chondrocyte in DNOAP group was higher than that in normal control group ( 28.1 ± 2.3 vs. 11.9 ± 0.7 ; P < 0.05 ). The expression of RANKL, TNF-α, IL-1β, and IL-6 protein in DNOAP group was higher than that in normal control group, whereas OPG and Aggrecan protein were lower than that in normal control group (both P < 0.05 ). FCM showed that the apoptotic rate of chondrocyte in DNOAP group was higher than that in normal control group ( P < 0.05 ). The RANKL/OPG ratio showed significant upward trend when the concentration of glucose was over than 15 mM. Conclusions. DNOAP patients tend to have severe destruction of articular cartilage and collapse of organelle structure including mitochondrion and endoplasm reticulum. Indicators of bone metabolism (RANKL and OPG) and inflammatory cytokines (IL-1β, IL-6, and TNF-α) play an important role in promoting the pathogenesis of DNOAP. The glucose concentration higher than 15 mM made the RANKL/OPG ratio change rapidly.

show abstract

“…In the context of pancreatic cancer, particular mitochondrial gene defects significantly influence tumor biology ( 17 , 18 , 61 , 62 ). Mutations in genes such as MT-ND4 (mitochondrial NADH dehydrogenase subunit 4) have been implicated in compromising the mitochondrial electron transport chain, leading to increased intracellular oxidative stress and destabilized energy metabolism ( 54 , 63 ).…”

Section: Mitochondrial Gene Defects and Pancreatic Cancer Developmentmentioning

confidence: 99%

Illuminating the immunological landscape: mitochondrial gene defects in pancreatic cancer through a multiomics lens

Chi,

Su,

Yan

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

This comprehensive review delves into the complex interplay between mitochondrial gene defects and pancreatic cancer pathogenesis through a multiomics approach. By amalgamating data from genomic, transcriptomic, proteomic, and metabolomic studies, we dissected the mechanisms by which mitochondrial genetic variations dictate cancer progression. Emphasis has been placed on the roles of these genes in altering cellular metabolic processes, signal transduction pathways, and immune system interactions. We further explored how these findings could refine therapeutic interventions, with a particular focus on precision medicine applications. This analysis not only fills pivotal knowledge gaps about mitochondrial anomalies in pancreatic cancer but also paves the way for future investigations into personalized therapy options. This finding underscores the crucial nexus between mitochondrial genetics and oncological immunology, opening new avenues for targeted cancer treatment strategies.

show abstract

Targeting mitochondrial dysfunctions in pancreatic cancer evokes new therapeutic opportunities

Cited by 8 publications

References 135 publications

Exploration of anti‐leukemic effect of soft coral‐derived 13‐acetoxysarcocrassolide: Induction of apoptosis via oxidative stress as a potent inhibitor of heat shock protein 90 and topoisomerase II

Exploration of anti‐leukemic effect of soft coral‐derived 13‐acetoxysarcocrassolide: Induction of apoptosis via oxidative stress as a potent inhibitor of heat shock protein 90 and topoisomerase II

Cartilage Damage Pathological Characteristics of Diabetic Neuropathic Osteoarthropathy

Illuminating the immunological landscape: mitochondrial gene defects in pancreatic cancer through a multiomics lens

Contact Info

Product

Resources

About