Evidence for role of transforming growth factor‐β in RRR‐a‐tocopheryl succinate‐induced apoptosis of human mda‐mb‐435 breast cancer cells

Yu, Weiping; Heim, Karen; Qian, Ming; Simmons‐Menchaca, Maria; Sanders, Bob G.; Kline, Kimberly

doi:10.1080/01635589709514537

Cited by 59 publications

(43 citation statements)

References 42 publications

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“…Additional support for the model comes from studies of human MDA-MB-435 breast cancer cells showing that VES-induced apoptosis is dependent on the induction of biologically active TGF-b (Yu et al, 1997b), and from studies showing that VES-treated cells express prolonged activated JNK and activated ATF-2 in addition to activated c-Jun (unpublished data). Future studies will address whether or not VES induced sustained upregulation of JNK, and c-Jun heterodimerized with activated ATF-2 are critical events in VES-induced apoptosis.…”

Section: Discussionmentioning

confidence: 98%

“…This activation of cJun is in contrast to rapid and transient expression of c-Jun which is a well established regulator of cell proliferation. Information provided in parenthesis and dotted lines is based on published data (conversion of latent to biologically active TGF-b, Yu et al, 1997b) and preliminary data (prolonged activation of JNK/SAPK stress signaling pathway and activation of ATF2 transcription factor). In this model, activated c-Jun, via dimerization with itself, other Fos/Jun family members of ATF2 cross family members, signals down-stream events that lead to apoptosis La Jolla, CA) was added, and the cells were incubated for 0.5, 1, 2 and 3 h).…”

Section: Actinomycin D Chase Analyses Of Mrna Stabilitymentioning

confidence: 99%

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c-Jun involvement in vitamin E succinate induced apoptosis of reticuloendotheliosis virus transformed avian lymphoid cells

Qian

Králová

et al. 1997

Oncogene

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Section: Discussionmentioning

confidence: 98%

Section: Actinomycin D Chase Analyses Of Mrna Stabilitymentioning

confidence: 99%

c-Jun involvement in vitamin E succinate induced apoptosis of reticuloendotheliosis virus transformed avian lymphoid cells

Qian

Králová

et al. 1997

Oncogene

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“…Kline's group first reported a role of JNK and c-jun in ␣-TOS-induced apoptosis. The VE analog up-regulated c-jun expression in different types of cancer cells (Qian et al, 1996;Yu et al, 1997aYu et al, , 1998. ␣-TOS-triggered apoptosis induced a prolonged increase in c-jun expression, and AP-1 transactivation and transfection of dominant-negative c-jun reduced ␣-TOS-mediated apoptosis.…”

Section: Nonmitochondrial Signaling Pathways and Apoptosis Induction mentioning

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

128

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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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“…Although the only structural difference between TS and ␣ -T is a succinyl ester moiety, their physicochemical properties are significantly different. TS has various biological activities that are not observed in ␣ -T, such as suppression of the function of transcriptional factor nuclear factor B (NF-B) [2][3][4][5], enhancement of nitric oxide production induced by lipopolysaccharide/interferon-␥ in rat vascular smooth muscle cells [ 6 ], suppression of the growth of various cancer cells [ 7 , 8 ], and induction of apoptosis in various cell lines [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Because of its higher cytotoxicity on various cancer cells than on normal cells [ 10 , 14 , 15 ], TS has attracted much attention as a new type of anti-cancer drug, and research on apoptosis induced by TS has been developing every year with a view to exploiting its anti-cancer effect.…”

Section: Introductionmentioning

confidence: 99%

Tocopheryl Succinate—Versatile Functions due to Its Unique Physicochemical Properties

Kogure

Fukuzawa

2004

J. Clin. Biochem. Nutr.

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Summary ␣ -Tocopheryl succinate (TS), a succinyl ester of ␣ -tocopherol ( ␣ -T), has no antioxidant activity, but it does have unique physicochemical properties and shows versatile biological functions. The physicochemical properties of TS affect the structure and function of lipid membranes, and the ability to form bilayer vesicles by itself suggests that TS can become a new carrier in the field of drug delivery systems. The ability to induce apoptosis is a most attractive property of TS. Because TS shows higher cytotoxicity on various cancer cells than on normal cells in vitro , prevents tumor growth, and extends survival in vivo , much attention has been paid to TS as a new type of anti-cancer drug. Activation of various signal transduction factors is also a well-known function of TS. In particular, protein kinase C (PKC), which acts in upstream in the signal transduction, is thought to play an important role in the effects of TS. Our theoretical computational study indicates that TS activates PKC by direct interaction with PKC due to its high structural flexibility.

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Evidence for role of transforming growth factor‐β in RRR‐a‐tocopheryl succinate‐induced apoptosis of human mda‐mb‐435 breast cancer cells

Cited by 59 publications

References 42 publications

c-Jun involvement in vitamin E succinate induced apoptosis of reticuloendotheliosis virus transformed avian lymphoid cells

c-Jun involvement in vitamin E succinate induced apoptosis of reticuloendotheliosis virus transformed avian lymphoid cells

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

Tocopheryl Succinate—Versatile Functions due to Its Unique Physicochemical Properties

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