Mitochondria in relation to cancer metastasis

Bhandary, Bidur; Marahatta, Anu; Kim, Hyung‐Ryong; Chae, Han-Jung

doi:10.1007/s10863-012-9464-x

Cited by 33 publications

(22 citation statements)

References 29 publications

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“…Suppression of oxidative stress has been considered to be a viable approach in treating cancer44. Thus, many anti-oxidant reagents like polyphenols, flavonoids and so on, are considered to be potential anti-cancer drug candidates45464748.…”

Section: Discussionmentioning

confidence: 99%

Shengmai Formula suppressed over-activated Ras/MAPK pathway in C. elegans by opening mitochondrial permeability transition pore via regulating cyclophilin D

Liu

Zhi

et al. 2016

Sci Rep

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Since about 30% of all human cancers contain mutationally activated Ras, down regulating the over-activation of Ras/MAPK pathway represents a viable approach for treating cancers. Over-activation of Ras/MAPK pathway is accompanied by accumulation of reactive oxygen species (ROS). One approach for developing anti-cancer drugs is to target ROS production and their accumulation. To test this idea, we have employed C. elegans of let-60 (gf) mutant, which contain over-activated let-60 (the homolog of mammalian ras) and exhibit tumor-like symptom of multivulva phenotype, to determine whether anti-oxidants can affect their tumor-like phenotype. Specifically we studied the effect of Shengmai formula (SM), a traditional Chinese medicine that has strong anti-oxidant activity, on the physiology of let-60 (gf) mutants. Unexpectedly, we found that SM treatment led to the opening of mitochondrial permeability transition pore by regulating cyclophilin D and then triggered oxidative stress and related signaling pathway activation, including p53, JNK, and p38/MAPK pathways. Finally, SM induced mitochondrial pathway of apoptosis and inhibited the tumor-like symptom of the multivulva phenotype of let-60(gf) mutants. Our results provide evidences to support that SM act as a pro-oxidant agent and could serve as a potential drug candidate for combating over-activated Ras-related cancer.

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Section: Discussionmentioning

confidence: 99%

Shengmai Formula suppressed over-activated Ras/MAPK pathway in C. elegans by opening mitochondrial permeability transition pore via regulating cyclophilin D

Liu

Zhi

et al. 2016

Sci Rep

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“…Regarding the cell signaling involved in the ER stress-induced retinal degeneration, the links between the UPR and other cellular regulatory processes remain largely unknown. Disruption of ER function broadly impacts other cellular pathways including oxidative stress, 10 cytosolic Ca 2+ -release 11 and inflammation. 12 Thus, all three UPR branches (PERK, IRE1a and ATF6) have been shown to mediate ‘cell autonomous' pro-inflammatory transcriptional programs and contribute substantially to progression of cystic fibrosis, metabolic disorders and intestinal bowel disease.…”

mentioning

confidence: 99%

An activated unfolded protein response promotes retinal degeneration and triggers an inflammatory response in the mouse retina

et al. 2014

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Recent studies on the endoplasmic reticulum stress have shown that the unfolded protein response (UPR) is involved in the pathogenesis of inherited retinal degeneration caused by mutant rhodopsin. However, the main question of whether UPR activation actually triggers retinal degeneration remains to be addressed. Thus, in this study, we created a mouse model for retinal degeneration caused by a persistently activated UPR to assess the physiological and morphological parameters associated with this disease state and to highlight a potential mechanism by which the UPR can promote retinal degeneration. We performed an intraocular injection in C57BL6 mice with a known unfolded protein response (UPR) inducer, tunicamycin (Tn) and examined animals by electroretinography (ERG), spectral domain optical coherence tomography (SD-OCT) and histological analyses. We detected a significant loss of photoreceptor function (over 60%) and retinal structure (35%) 30 days post treatment. Analysis of retinal protein extracts demonstrated a significant upregulation of inflammatory markers including interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and IBA1. Similarly, we detected a strong inflammatory response in mice expressing either Ter349Glu or T17M rhodopsin (RHO). These mutant rhodopsin species induce severe retinal degeneration and T17M rhodopsin elicits UPR activation when expressed in mice. RNA and protein analysis revealed a significant upregulation of pro- and anti-inflammatory markers such as IL-1β, IL-6, p65 nuclear factor kappa B (NF-kB) and MCP-1, as well as activation of F4/80 and IBA1 microglial markers in both the retinas expressing mutant rhodopsins. We then assessed if the Tn-induced inflammatory marker IL-1β was capable of inducing retinal degeneration by injecting C57BL6 mice with a recombinant IL-1β. We observed ~19% reduction in ERG a-wave amplitudes and a 29% loss of photoreceptor cells compared with control retinas, suggesting a potential link between pro-inflammatory cytokines and retinal pathophysiological effects. Our work demonstrates that in the context of an established animal model for ocular disease, the persistent activation of the UPR could be responsible for promoting retinal degeneration via the UPR-induced pro-inflammatory cytokine IL-1β.

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“…Androgen activates the cleavage of SREBP by increasing the (19) AKT/GSK3β (20) expression of SCAP and INSIG (57). SREBP1 also increases reactive oxygen species (ROS) production (101) inducing tumor progression (102). A similar role of progesterone and EGF on SREBP cleavage and expression was reported in breast cancer cells (22,65,67).…”

Section: Implication Of Other Lipogenic Genesmentioning

confidence: 85%

Lipogenesis in cancer progression (Review)

Mounier

Bouraoui

Rassart

2014

International Journal of Oncology

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Abstract. In normal tissues, energy-providing lipids come principally from circulating lipids. However, in growing tumors, energy supply is mainly provided by lipids coming from de novo synthesis. It is not surprising to see elevated expression of several lipogenic genes in tumors from different origins. The role of lipogenic genes in the establishment of the primary tumor has been clearly established. A large number of studies demonstrate a role of fatty acid synthase in the activation of cell cycle and inhibition of apoptosis in tumor cells. Other lipogenic genes such as the acetyl CoA carboxylase (ACC) and the stearoyl CoA desaturase 1 (SCD1) are highly expressed in primary tumors and also appear to play a role in their development. However, the role of lipogenesis in the metastatic process is less clear. In the present review, we aim to present the most recent evidences for the key role of lipogenic enzymes in the metastatic process and in epithelial to mesenchymal transition.

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Mitochondria in relation to cancer metastasis

Cited by 33 publications

References 29 publications

Shengmai Formula suppressed over-activated Ras/MAPK pathway in C. elegans by opening mitochondrial permeability transition pore via regulating cyclophilin D

Shengmai Formula suppressed over-activated Ras/MAPK pathway in C. elegans by opening mitochondrial permeability transition pore via regulating cyclophilin D

An activated unfolded protein response promotes retinal degeneration and triggers an inflammatory response in the mouse retina

Lipogenesis in cancer progression (Review)

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