Structural characteristic of terminal dicarboxylic moiety required for apoptogenic activity of α-tocopheryl esters

Kogure, Kentaro; Hama, Susumu; Kisaki, M.; Takemasa, Hideaki; Tokumura, Akira; Suzuki, Ichirô; Fukuzawa, Kenji

doi:10.1016/j.bbagen.2004.03.001

Cited by 32 publications

(33 citation statements)

References 19 publications

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“…The number of cell deaths increased with the increase of concentration of a-tocopheryl esters, and the order of their cytotoxicity was TO>TM>TS at the same concen tration. Similar results were observed in our previous experiment using mouse breast cancer cells C1271 (22). Effects of antioxidants on a-tocopheryl ester induced death of B16-F1 cells W e previously reported that superoxide (O2-) gener ated by NADPH-oxidase is responsible for TS-induced apoptosis in rat vascular smooth muscle cells (12) .…”

Section: Resultssupporting

confidence: 77%

Cytotoxicity of .ALPHA.-Tocopheryl Succinate, Malonate and Oxalate in Normal and Cancer Cells In Vitro and Their Anti-Cancer Effects on Mouse Melanoma In Vivo

Kogure

Manabe

Suzuki

et al. 2005

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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Section: Resultssupporting

confidence: 77%

Cytotoxicity of .ALPHA.-Tocopheryl Succinate, Malonate and Oxalate in Normal and Cancer Cells In Vitro and Their Anti-Cancer Effects on Mouse Melanoma In Vivo

Kogure

Manabe

Suzuki

et al. 2005

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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“…Even greater apoptogenic activity has been observed for unsaturated dicarboxylic acids like ␣-tocopheryl maleate (3) (Birringer et al, 2003) and ␣-tocopheryl fumarate (J. Neuzil, unpublished data). Increasing the chain length of the dicarboxylic acid led to decreased activity as shown for glutaric acid (5) and methylated glutaric acids (6-8) (Birringer et al, 2003), with pimelic acid (24) (Kogure et al, 2004) exhibiting no activity at all.…”

Section: Redox-silent Tocopherol Derivatives: Modifications Of the Fumentioning

confidence: 99%

Vitamin E Analogs, a Novel Group of “Mitocans,” as Anticancer Agents: The Importance of Being Redox-Silent

Neužil¹,

Tomasetti²,

Zhao³

et al. 2007

Mol Pharmacol

126

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The search for a selective and efficient anticancer agent for treating all neoplastic disease has yet to deliver a universally suitable compound(s). The majority of established anticancer drugs either are nonselective or lose their efficacy because of the constant mutational changes of malignant cells. Until recently, a largely neglected target for potential anticancer agents was the mitochondrion, showing a considerable promise for future clinical applications. Vitamin E (VE) analogs, epitomized by ␣-tocopheryl succinate, belong to the group of "mitocans" (mitochondrially targeted anticancer drugs). They are selective for malignant cells, cause destabilization of their mitochondria, and suppress cancer in preclinical models. This review focuses on our current understanding of VE analogs in the context of their proapoptotic/anticancer efficacy and suggests that their effect on mitochondria may be amplified by modulation of alternative pathways operating in parallel. We show here that the analogs of VE that cause apoptosis (which translates into their anticancer efficacy) generally do not possess antioxidant (redox) activity and are prototypical of the mitocan group of anticancer compounds. Therefore, by analogy to Oscar Wilde's play The Importance of Being Earnest, we use the motto in the title "the importance of being redox-silent" to emphasize an essentially novel paradigm for cancer therapy, in which redoxsilence is a prerequisite property for most of the anticancer activities described in this communication.Despite advances in molecular medicine, the third millennium has borne witness to neoplastic disease becoming a major cause for mortality in developed countries. Moreover, fast-growing economies in countries like India and China are likely to be severely affected by cancer in a decade or so as a result of heavy industrialization. Certain types of cancer, such as malignant mesothelioma (MM), seem to remain beyond the realms of treatment. In many other cases, mutations arise in the tumors, seriously compromising the outcome of the therapy. For example, in breast cancer, in which a high frequency of overexpression of the tyrosine receptor kinase erbB2 occurs, this is often associated with resistance to chemotherapy (Xia et al., 2006). We are therefore in need of treatment modalities that would overcome these problems and that are efficient, selective, and readily available to all Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org. doi:10.1124/mol.106.030122.ABBREVIATIONS: MM, malignant mesothelioma; BH, Bcl-2 homology; DHFR, dihydrofolate reductase; DR, death receptor; ERK, extracellular signal-regulated protein kinase; FLIP, Fas-associated death domain-like interleukin-1␤-converting enzyme-inhibitory protein; IAP, inhibitor of apoptosis protein; IB, inhibitory subunit of nuclear factor B; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MPTP, mitochondrial permeability transition pore; MTX, methotrexate; NFB, nuclear factor-B; O...

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“…Furthermore, Tafazoli et al (2005) also showed that pro-oxidant radicals of α-tocopherol analogues can cause intracellular LPO, glutathione (GSH) oxidation, and cytotoxicity. Some α-tocopherol analogues such as α-tocopheryl phosphates and α-tocopheryl esters were found to have cytotoxic effects in VSMCs (Kogure et al, 2004;Munteanu et al, 2004), whereas PMC has no cytotoxicity in VSMCs ( Figure 2D). PMC is the most effective antioxidant with the lowest pro-oxidant activity and may have therapeutic advantages over the other α-tocopherol analogues (Tafazoli et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effect of PMC, a potent hydrophilic α-tocopherol derivative, on vascular smooth muscle cell proliferation: The pivotal role of PKC-α translocation

Chang

Lee

Chiang

et al. 2010

Pharmaceutical Biology

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Structural characteristic of terminal dicarboxylic moiety required for apoptogenic activity of α-tocopheryl esters

Cited by 32 publications

References 19 publications

Cytotoxicity of .ALPHA.-Tocopheryl Succinate, Malonate and Oxalate in Normal and Cancer Cells In Vitro and Their Anti-Cancer Effects on Mouse Melanoma In Vivo

Cytotoxicity of .ALPHA.-Tocopheryl Succinate, Malonate and Oxalate in Normal and Cancer Cells In Vitro and Their Anti-Cancer Effects on Mouse Melanoma In Vivo

Vitamin E Analogs, a Novel Group of “Mitocans,” as Anticancer Agents: The Importance of Being Redox-Silent

Inhibitory effect of PMC, a potent hydrophilic α-tocopherol derivative, on vascular smooth muscle cell proliferation: The pivotal role of PKC-α translocation

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