Mitochondrial division inhibitor (mdivi-1) inhibits proliferation and epithelial-mesenchymal transition via the NF-κB pathway in thyroid cancer cells

Zhang, Lin; Sun, Lei; Wang, Lirong; Wang, Juan; Wang, Dan; Jiang, Jue; Zhang, Jinhui; Zhou, Qiongqiong

doi:10.1016/j.tiv.2023.105552

Cited by 6 publications

(5 citation statements)

References 39 publications

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“…Mdivi-1, a mitochondrial division inhibitor, is well-known for its anti-proliferative effects on various tumor cells in vitro and in vivo 16 , 17 , 27 . Due to its promising therapeutic potential in inhibiting tumor growth, mdivi-1 is considered an attractive candidate for treating solid tumors 28 .…”

Section: Resultsmentioning

confidence: 99%

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Mitochondrial division inhibitor (mdivi-1) induces extracellular matrix (ECM)-detachment of viable breast cancer cells by a DRP1-independent mechanism

Silva-Pavez,

Mendoza,

Morgado-Cáceres

et al. 2024

Sci Rep

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Increasing evidence supports the hypothesis that cancer progression is under mitochondrial control. Mitochondrial fission plays a pivotal role in the maintenance of cancer cell homeostasis. The inhibition of DRP1, the main regulator of mitochondrial fission, with the mitochondrial division inhibitor (mdivi-1) had been associated with cancer cell sensitivity to chemotherapeutics and decrease proliferation. Here, using breast cancer cells we find that mdivi-1 induces the detachment of the cells, leading to a bulk of floating cells that conserved their viability. Despite a decrease in their proliferative and clonogenic capabilities, these floating cells maintain the capacity to re-adhere upon re-seeding and retain their migratory and invasive potential. Interestingly, the cell detachment induced by mdivi-1 is independent of DRP1 but relies on inhibition of mitochondrial complex I. Furthermore, mdivi-1 induces cell detachment rely on glucose and the pentose phosphate pathway. Our data evidence a novel DRP1-independent effect of mdivi-1 in the attachment of cancer cells. The generation of floating viable cells restricts the use of mdivi-1 as a therapeutic agent and demonstrates that mdivi-1 effect on cancer cells are more complex than anticipated.

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Section: Resultsmentioning

confidence: 99%

“…This molecule has shown great potential as a therapeutic agent in cancer treatment. Studies have shown that mdivi-1 can decrease proliferation in thyroid and lung cancer cells 16 , 17 and induce apoptosis in pancreatic stem cancer cells 18 . However, recent research has identified complex I as a new target of mdivi-1 19 .…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial division inhibitor (mdivi-1) induces extracellular matrix (ECM)-detachment of viable breast cancer cells by a DRP1-independent mechanism

Silva-Pavez,

Mendoza,

Morgado-Cáceres

et al. 2024

Sci Rep

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show abstract

“…Mdivi-1, a mitochondrial division inhibitor, is well-known for its anti-proliferative effects on various tumor cells in vitro and in vivo 17,18,29 . Due to its promising therapeutic potential in inhibiting tumor growth, mdivi-1 is considered an attractive candidate for treating solid tumors 30 .…”

Section: Mdivi-1 Induces Detachment Of Viable Mcf-7 and Mda-mb-231 Br...mentioning

confidence: 99%

“…This molecule has shown great potential as a therapeutic agent in cancer treatment. Studies have shown that mdivi-1 can decrease proliferation in thyroid and lung cancer cells 17,18 and induce apoptosis in pancreatic stem cancer cells 19 . However, recent research has identified complex I as a new target of mdivi-1 20 .…”

mentioning

confidence: 99%

Mitochondrial division inhibitor (mdivi-1) induces extracellular matrix (ECM)-detachment of viable breast cancer cells by a DRP1-independent mechanism

Silva-Pavez,

Mendoza,

Morgado-Cáceres

et al. 2024

Preprint

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Increasing evidence supports the hypothesis that cancer progression is under mitochondrial control. Mitochondrial fission plays a pivotal role in the maintenance of cancer cell homeostasis. The inhibition of DRP1, the main regulator of mitochondrial fission, with the mitochondrial division inhibitor (mdivi-1) had been associated with cancer cell sensitivity to chemotherapeutics and decreased proliferation. Here, using breast cancer cells we find that mdivi-1 induces the detachment of the cells, leading to a bulk of floating cells that conserve their viability. Despite a decrease in their proliferative and clonogenic capabilities, these floating cells maintain the capacity to re-adhere upon re-seeding and retain their migratory and invasive potential. Interestingly, the cell detachment induced by mdivi-1 is independent of DRP1 but relies on inhibition of mitochondrial complex I. Furthermore, mdivi-1 induces cell detachment rely on glucose and the pentose phosphate pathway (PPP). Our data evidence a novel DRP1-independent effect of mdivi-1 in the attachment of cancer cells. The generation of floating viable cells restricts the use of mdivi-1 as a therapeutic agent and demonstrates that mdivi-1 effect on cancer cells are more complex than anticipated.

show abstract

“…An increased expression of Drp1 and a downregulation of Mfn-2 have been observed in endometrial cancer, resulting in an imbalance of mitochondrial dynamics towards fission [ 93 ]. The selective inhibitor of Drp1, Mdivi-1, decreased fission, oxidative metabolism, and impaired cell proliferation in different cancer cell lines [ 94 , 95 ]. Moreover, two Ellipticine analogues, namely Drpitor1 and Drpitor1a, displayed a selective inhibitory activity against Drp1, which impaired mitochondrial fission; this resulted in the inhibition of cancer cell proliferation and apoptosis in both cancer cell cultures and xenograft mouse models [ 96 ].…”

Section: Molecules Targeting Mitochondrial Homeostasismentioning

confidence: 99%

Mitochondria Deregulations in Cancer Offer Several Potential Targets of Therapeutic Interventions

Musicco

Signorile

Pesce

et al. 2023

IJMS

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Mitochondria play a key role in cancer and their involvement is not limited to the production of ATP only. Mitochondria also produce reactive oxygen species and building blocks to sustain rapid cell proliferation; thus, the deregulation of mitochondrial function is associated with cancer disease development and progression. In cancer cells, a metabolic reprogramming takes place through a different modulation of the mitochondrial metabolic pathways, including oxidative phosphorylation, fatty acid oxidation, the Krebs cycle, glutamine and heme metabolism. Alterations of mitochondrial homeostasis, in particular, of mitochondrial biogenesis, mitophagy, dynamics, redox balance, and protein homeostasis, were also observed in cancer cells. The use of drugs acting on mitochondrial destabilization may represent a promising therapeutic approach in tumors in which mitochondrial respiration is the predominant energy source. In this review, we summarize the main mitochondrial features and metabolic pathways altered in cancer cells, moreover, we present the best known drugs that, by acting on mitochondrial homeostasis and metabolic pathways, may induce mitochondrial alterations and cancer cell death. In addition, new strategies that induce mitochondrial damage, such as photodynamic, photothermal and chemodynamic therapies, and the development of nanoformulations that specifically target drugs in mitochondria are also described. Thus, mitochondria-targeted drugs may open new frontiers to a tailored and personalized cancer therapy.

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Mitochondrial division inhibitor (mdivi-1) inhibits proliferation and epithelial-mesenchymal transition via the NF-κB pathway in thyroid cancer cells

Cited by 6 publications

References 39 publications

Mitochondrial division inhibitor (mdivi-1) induces extracellular matrix (ECM)-detachment of viable breast cancer cells by a DRP1-independent mechanism

Mitochondrial division inhibitor (mdivi-1) induces extracellular matrix (ECM)-detachment of viable breast cancer cells by a DRP1-independent mechanism

Mitochondrial division inhibitor (mdivi-1) induces extracellular matrix (ECM)-detachment of viable breast cancer cells by a DRP1-independent mechanism

Mitochondria Deregulations in Cancer Offer Several Potential Targets of Therapeutic Interventions

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