Cyclovirobuxine D Induced-Mitophagy through the p65/BNIP3/LC3 Axis Potentiates Its Apoptosis-Inducing Effects in Lung Cancer Cells

Zeng, Cheng; Zou, Tingting; Qu, Junyan; Xu, Chen; Zhang, Suping; Lin, Zhenghong

doi:10.3390/ijms22115820

Cited by 24 publications

(15 citation statements)

References 44 publications

(49 reference statements)

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“…The understanding of BNIP3 in the regulation of mitophagy is not only to regulate Beclin-1 through BH3 domain to activate autophagy. BNIP3 also activates mitophagy by inducing MMP loss or depolarization and directly interacting with autophagy connecting molecule LC3 (Zeng et al 2021 ; Shi et al 2014 ). When autophagy is activated, the cytoplasmic LC3B-I is cleaved, fatty and inserted into the autophagosome membrane as LC3-II.…”

Section: Discussionmentioning

confidence: 99%

BNIP3 mediates the different adaptive responses of fibroblast-like synovial cells to hypoxia in patients with osteoarthritis and rheumatoid arthritis

Deng

Wang

et al. 2022

Mol Med

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Background Hypoxia is one of the important characteristics of synovial microenvironment in rheumatoid arthritis (RA), and plays an important role in synovial hyperplasia. In terms of cell survival, fibroblast-like synovial cells (FLSs) are relatively affected by hypoxia. In contrast, fibroblast-like synovial cells from patients with RA (RA-FLSs) are particularly resistant to hypoxia-induced cell death. The purpose of this study was to evaluate whether fibroblast-like synovial cells in patients with osteoarthritis (OA-FLSs) and RA-FLSs have the same adaptation to hypoxia. Methods CCK-8, flow cytometry and BrdU were used to detect the proliferation of OA-FLSs and RA-FLSs under different oxygen concentrations. Apoptosis was detected by AV/PI, TUNEL and Western blot, mitophagy was observed by electron microscope, laser confocal microscope and Western blot, the state of mitochondria was detected by ROS and mitochondrial membrane potential by flow cytometry, BNIP3 and HIF-1α were detected by Western blot and RT-qPCR. The silencing of BNIP3 was achieved by stealth RNA system technology. Results After hypoxia, the survival rate of OA-FLSs decreased, while the proliferation activity of RA-FLSs further increased. Hypoxia induced an increase in apoptosis and inhibition of mitophagy in OA-FLSs, but not in RA-FLSs. Hypoxia led to a more lasting adaptive response. RA-FLSs displayed a more significant increase in the expression of genes transcriptionally regulated by HIF-1α. Interestingly, they showed higher BNIP3 expression than OA-FLSs, and showed stronger mitophagy and proliferation activities. BNIP3 siRNA experiment confirmed the potential role of BNIP3 in the survival of RA-FLSs. Inhibition of BNIP3 resulted in the decrease of cell proliferation, mitophagy and the increase of apoptosis. Conclusion In summary, RA-FLSs maintained intracellular redox balance through mitophagy to promote cell survival under hypoxia. The mitophagy of OA-FLSs was too little to maintain the redox balance of mitochondria, resulting in apoptosis. The difference of mitophagy between OA-FLSs and RA-FLSs under hypoxia is mediated by the level of BNIP3 expression.

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Section: Discussionmentioning

confidence: 99%

BNIP3 mediates the different adaptive responses of fibroblast-like synovial cells to hypoxia in patients with osteoarthritis and rheumatoid arthritis

Deng

Wang

et al. 2022

Mol Med

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“…It forms a stable homodimer following stress signals and translocates to the outer mitochondrial membrane ( Fu et al, 2020 ; Kubli et al, 2008 ). BNIP3 has a LIR motif at its N-terminal region interaction with LC3, leading to mitophagy ( Zeng et al, 2021 ). NIX is a homology of BNIP3, promoting the selective degradation of mitochondria ( Da et al, 2021 ).…”

Section: Endothelial Mitophagy and Atherosclerosismentioning

confidence: 99%

Mitochondrial dysfunction in vascular endothelial cells and its role in atherosclerosis

Fang

Xian

et al. 2022

Front. Physiol.

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The mitochondria are essential organelles that generate large amounts of ATP via the electron transport chain (ECT). Mitochondrial dysfunction causes reactive oxygen species accumulation, energy stress, and cell death. Endothelial mitochondrial dysfunction is an important factor causing abnormal function of the endothelium, which plays a central role during atherosclerosis development. Atherosclerosis-related risk factors, including high glucose levels, hypertension, ischemia, hypoxia, and diabetes, promote mitochondrial dysfunction in endothelial cells. This review summarizes the physiological and pathophysiological roles of endothelial mitochondria in endothelial function and atherosclerosis.

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“…Cyclovirobuxine D (CVB‐D) is the major active component of Buxus microphylla, which is mainly used in the treatment of cardiovascular and cerebrovascular diseases (Bian et al, 2021; Yu, Fang, Lü, Xu, & Lu, 2011). In recent years, more and more evidence has suggested that CVB‐D may have inhibitory effects on various tumors (Lu et al, 2014; Zeng et al, 2021; Zhou et al, 2020). Besides, CVB‐D inhibits CRC cell growth and decreases angiogenesis via the CTHRC1‐AKT/ERK‐Snail signaling pathway, especially microvasculature (Jiang et al, 2020).…”

Section: Natural Anti‐gic Angiogenic Compounds Derived From Plantsmentioning

confidence: 99%

Pull the plug: Anti‐angiogenesis potential of natural products in gastrointestinal cancer therapy

Zhao

Wang

et al. 2022

Phytotherapy Research

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Gastrointestinal cancer (GIC), including gastric cancer and colorectal cancer, is a common malignant tumor originating from the gastrointestinal epithelium. Although the pathogenesis of GIC has not been fully elucidated, angiogenesis is recognized as the key pathological basis for the growth, invasion and metastasis of cancer cells, and GIC angiogenesis is closely related to vascular endothelial growth factor family, hypoxia‐inducible factor family, fibroblast growth factor family and matrix metalloproteinase family. Recently, many natural products have shown a wide range of pharmacological biological activities against GIC. In this review, the effects and mechanisms of natural compounds on the angiogenesis of gastric and colorectal cancer were summarized. The results show that some natural compounds, especially gallic catechin gallate, astragaloside and curcumin, can effectively inhibit angiogenesis; the HIF‐1α/VEGF, COX‐2/PGE2, HGF/c‐Met and PI3K/Akt/mTOR are involved in these inhibition effects. This review examines the anti‐angiogenesis potential of natural products in the GIC treatment and provides clues to the development of vascular targeted agents.

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Cyclovirobuxine D Induced-Mitophagy through the p65/BNIP3/LC3 Axis Potentiates Its Apoptosis-Inducing Effects in Lung Cancer Cells

Cited by 24 publications

References 44 publications

BNIP3 mediates the different adaptive responses of fibroblast-like synovial cells to hypoxia in patients with osteoarthritis and rheumatoid arthritis

BNIP3 mediates the different adaptive responses of fibroblast-like synovial cells to hypoxia in patients with osteoarthritis and rheumatoid arthritis

Mitochondrial dysfunction in vascular endothelial cells and its role in atherosclerosis

Pull the plug: Anti‐angiogenesis potential of natural products in gastrointestinal cancer therapy

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