BackgroundMitochondrial homeostasis has been increasingly viewed as a potential target of cancer therapy, and mitochondrial fission is a novel regulator of mitochondrial function and apoptosis. The aim of our study was to determine the detailed role of mitochondrial fission in SW837 colorectal cancer cell viability, mobility and proliferation. In addition, the current study also investigated the therapeutic impact of Tanshinone IIA (Tan IIA), a type of anticancer adjuvant drug, on cancer mitochondrial homeostasis.ResultsThe results of our data illustrated that Tan IIA promoted SW837 cell death, impaired cell migration and mediated cancer proliferation arrest in a dose-dependent manner. Functional investigation exhibited that Tan IIA treatment evoked mitochondrial injury, as witnessed by mitochondrial ROS overproduction, mitochondrial potential collapse, antioxidant factor downregulation, mitochondrial pro-apoptotic protein upregulation, and caspase-9-dependent apoptotic pathway activation. Furthermore, we confirmed that Tan IIA mediated mitochondrial damage by activating mitochondrial fission, and the inhibition of mitochondrial fission abrogated the proapoptotic effects of Tan IIA on SW837 cells. To this end, our results demonstrated that Tan IIA modulated mitochondrial fission via the JNK-Mff pathways. The blockade of the JNK-Mff axis inhibited Tan IIA-mediated mitochondrial fission and promoted the survival of SW837 cells.ConclusionsAltogether, our results identified mitochondrial fission as a new potential target to control cancer viability, mobility and proliferation. Furthermore, our findings demonstrate that Tan IIA is an effective drug to treat colorectal cancer by activating JNK-Mff-mitochondrial fission pathways.Electronic supplementary materialThe online version of this article (10.1186/s12860-018-0174-z) contains supplementary material, which is available to authorized users.
Objective: We investigated the effect of icariin (ICA) combined with Panax notoginseng saponins (PNS) on intestinal microbiota and hippocampal protein expression in amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice, a model of Alzheimer's disease (AD). Methods: Transgenic mice were treated with icariin and PNS. The Morris water maze (MWM) was used to assess spatial memory, and the gut microbiota and differential protein expression in the hippocampus were investigated using high-throughput screening techniques. Differential protein expression was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Results: The MWM results showed that the mice treated with the medium dose of ICA +PNS spent significantly more time in the target quadrant compared with the AD group. Bacterial diversity was the lowest in the AD group, with significantly greater diversity in the ICA + PNS treatment group. Three proteins were selected for proteomic analysis, and qRT-PCR and Western blot were used to detect the expression of 2ʹ-5ʹ-oligoadenylate synthetase ubiquitin like 1 (Oasl1), trichoplein keratin filament-binding protein (TCHP), and tumor necrosis factor receptor associated 3-interacting protein 1 (MIPT3). Compared with control mice, MIPT3 expression was increased and Oasl1 and TCHP were reduced in the AD group. These abnormal protein expressions tended to normalization after treatment with medium dose of ICA and PNS. Conclusion: Treatment with ICA and PNS ameliorated memory impairment in an AD mouse model. The mechanisms may be related to modulation of the intestinal microbiota and expression of Oasl1, TCHP, and MIPT3.
Yizhijiannao granules have been shown to improve cognitive function in Alzheimer's disease patients. The present study sought to explore the mechanisms involved in the cognitive enhancing effects of Yizhijiannao granule. Senescence-accelerated mouse prone 8 mice with learning and memory disorders were intragastrically treated with Yizhijiannao granule for 8 weeks. Mice intragastrically treated with double distilled water for 8 weeks were considered as the control group. 2D gel electrophoresis was used to isolate total protein from the temporal lobe of senescence-accelerated mouse prone 8 mice, and differential protein spots were obtained by mass spectrometry. Thirty-seven differential protein spots were found in the temporal lobe area of both groups. Ten protein spots were identified: high mobility group box 1, dimethylarginine dimethylaminohydrolase-1, neuroglobin, hemoglobin beta adult major chain, peroxiredoxin-6, cofilin-1, flotillin 1, peptidylprolyl isomerase A, voltage-dependent anion channel-2 and chaperonin containing TCP1, and subunit 2. Among other functions, these proteins are separately involved in the regulation of amyloid beta production, oxidative stress, neuroinflammation, regulation of tau phosphorylation, and regulation of neuronal apoptosis. Our results revealed that Yizhijiannao granule can regulate the expression of various proteins in the temporal lobe of senescence-accelerated mouse prone 8 mice, and may be therapeutically beneficial for the treatment of Alzheimer's disease.
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