Mitochondrially Targeted Vitamin E Succinate Modulates Expression of Mitochondrial DNA Transcripts and Mitochondrial Biogenesis

Abstract

Our data indicate a novel, selective anti-cancer activity of compounds that act by targeting mitochondria of cancer cells, inducing significant alterations in mitochondrial function associated with transcription of mtDNA-coded genes. These changes subsequently result in the arrest of cell proliferation.

Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

“…428 The antitumor effects of MitoVE 11 S were also linked to its antiangiogenic activity, and inhibition of mitochondrial DNA transcription and mitogenesis were observed both in vitro and in vivo. 429,430 Interestingly, MitoVE 11 S efficiently blocked the proliferation of both VES-sensitive and VES-resistant cell lines. 431 Although it was assumed that the succinate moiety was important for interaction with mitochondrial complex II, the susceptibility of mitochondria-targeted vitamin E succinate (MitoVES) to intracellular hydrolysis, and the anticancer effects of MitoVE 11 S were not compared with its hydrolyzed analog, MitoVE 11 .…”

The interplay of circulating tumor DNA and chromatin modification, therapeutic resistance, and metastasis

“…For example, mitochondrial proteins, such as Lon protease, Mitofusin-2, and TFAM, among others, may be potential therapeutic targets [157] for bladder cancer. Mitochondrially targeted vitamin E succinate (MitoVES) [158] can influence mtDNA transcripts, inhibit mitochondrial respiration, reduce the generation of reactive oxygen species, and thus suppress the proliferation of cancer cells. A photochemotherapy (PCT) [159] strategy targeting mtDNA using near-infrared (NIR)-assisted tumor-specific Fenton reactions has also been proposed.…”

Selective Disruption of Respiratory Supercomplexes as a New Strategy to Suppress Her2high Breast Cancer

“…Cells were seeded on glass-bottom microscopy dishes coated with poly-L-lysine. Images were recorded the third day after seeding using 63x oil immersion lens of the SP5 confocal microscope (Leica Microsystems, Wetzlar, Germany) equipped with a heated CO 2 incubator as described in detail before (53). Time-lapse images were recorded every 5 min with the first image taken 5 min before adding the drug.…”