RRR‐α‐tocopheryl succinate enhances TGF‐β1, ‐β2, and ‐β3and TGF‐βR‐II expression by human MDA‐MB‐435 breast cancer cells

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

doi:10.1080/01635589609514480

Cited by 29 publications

(18 citation statements)

References 44 publications

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“…As mentioned in the Introduction, VES appears to activate at least two apoptotic-triggering pathways in cells: the TGF-β and Fas signaling pathways [5][6][7]9,11,14]. Based on previously published data [11][12][13] and the data presented in this paper showing activation of JNK, we have developed the following working hypothesis for VES-induced apoptosis.…”

Section: Amentioning

confidence: 85%

“…VES is a potent inhibitor of human breast cancer cell growth in vitro, inducing breast cancer cells to undergo DNA synthesis arrest and apoptosis [2,3,5,9,11,12,14,40]. In contrast, VES does not induce apoptosis of either normal human mammary epithelial cells (unpublished data) or immortalized but nontumorigenic human mammary MCF-10 cells [3].…”

Section: Discussionmentioning

confidence: 96%

“…Growth inhibition by VES is attributed to cell-cycle blockages [2], induced cellular differentiation [4], increased expression of biologically active transforming growth factor-βs (TGF-βs) and TGF-βR-II expression [5][6][7][8][9], and VES-triggered apoptosis [7][8][9][10][11][12][13][14][15]. VES is noteworthy not only for its antiproliferative effects on tumor cells but also for its non-toxic effect on normal cell types [1,16].…”

Section: Introductionmentioning

confidence: 99%

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RRR-α-tocopheryl succinate induction of prolonged activation of c-jun amino-terminal kinase and c-jun during induction of apoptosis in human MDA-MB-435 breast cancer cells

Simmons-Menchaca

You

et al. 1998

Mol. Carcinog.

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We have demonstrated that RRR-alpha-tocopheryl succinate (10 microg/mL vitamin E succinate (VES) treatment of estrogen receptor-negative MDA-MB-435 human breast cancer cells induces 9, 19, 51, and 72% apoptotic cells on days 1-4, respectively, after treatment, which involves transforming growth factor-beta signaling. Here, we show that VES-triggered apoptosis of MDA-MB-435 cells induced prolonged elevated expression of c-jun mRNA and protein (neither of which was caused by major increases in stability) and also induced enhanced activator protein-1 (AP-1) binding to the consensus DNA oligomer. Furthermore, VES treatments resulted in increased AP-1 transactivation activity, as measured with an AP-1 promoter/luciferase reporter construct and by the measurement of increased mRNA expression of the AP-1-dependent endogenous gene collagenase. Evidence of VES-induced involvement of the c-jun amino-terminal kinase in these AP-1-dependent events was suggested by data showing prolonged activity of this kinase, as measured by a kinase assay using glutathione S-transferase-c-jun as the substrate. The c-jun-dependent transcriptional activity was verified by cotransfection of a chimeric transcription factor having a galactose 4 DNA-binding domain coupled with the transactivation domain of c-jun plus the reporter plasmid 5X GAL4-luciferase. MDA-MB-435 cells infected with an adenovirus expression vector containing the TAM-67 sequence for dominant/negative-acting mutant c-jun or transiently transfected with c-jun antisense exhibited a 50-77% reduction in VES-mediated apoptosis as compared with control adenovirus-infected or control sense oligomer-transfected cells.

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Section: Amentioning

confidence: 85%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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RRR-α-tocopheryl succinate induction of prolonged activation of c-jun amino-terminal kinase and c-jun during induction of apoptosis in human MDA-MB-435 breast cancer cells

Simmons-Menchaca

You

et al. 1998

Mol. Carcinog.

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“…12]. Important to note here is that aTS treatment of tumor cells results in increased concentrations of biologically active TGF-b and an increase in TGF-b receptor expression [6,8]. Besides the TGF-b signaling pathway, the Fas/Fas ligand pathway also contributes to aTS-induced apoptosis in human breast cancer cells [13,14].…”

mentioning

confidence: 99%

Inhibition of lung carcinoma cell growth by high density lipoprotein-associated ?-tocopheryl-succinate

Hrzenjak

Reicher

Wintersperger

et al. 2004

CMLS, Cell. Mol. Life Sci.

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Alpha-tocopheryl-succinate (alphaTS) is a synthetic, anti-neoplastic derivative of alpha-tocopherol. Here we studied the effects of free and high-density lipoprotein subclass 3 (HDL3)-associated alphaTS on the growth of human (A549) and mouse Lewis (LL2) lung carcinoma cells. Both free and HDL3-associated alphaTS inhibited A549 growth in a time- and concentration-dependent manner. Treatment of A549 cells with alphaTS-enriched HDL3 led to DNA fragmentation and a time-dependent decrease in immunoreactivity of poly(ADP-ribose)polymerase. Uptake experiments revealed a high capacity for selective alphaTS uptake in excess of holoparticle endocytosis. Overexpression of scavenger receptor class B, type I (SR-BI), the prime receptor mediating selective lipid uptake, in A549 cells resulted in significantly increased selective alphaTS uptake, a finding associated with complete cellular growth arrest. The present in vitro findings were verified in an in vivo model: tumor inoculation in C57BL6 was performed with either wild-type, beta-galactosidase- or SR-BI-overexpressing LL2 cells. After tumor inoculation, the animals received six consecutive intravenous injections of alphaTS. This experimental setup resulted in significantly reduced tumor burden in animals that were inoculated with SR-BI-overexpressing LL2 cells but not in animals inoculated with wild-type or beta-galactocidase-transfected cells. Based on our in vitro and in vivo findings, we propose that SR-BI could provide a novel route for HDL3-mediated drug delivery of anti-neoplastic drugs.

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“…The antiproliferative activity of TS has been shown to involve the induction of transforming growth factor-h responsiveness (10,23,24), increased expression of the cyclin-dependent kinase inhibitor p21 Waf1/Cip1 (25 -27), and inhibition of the activity of the cell cycle progression transcription factor E2F (28 -30). The proapoptotic activity of TS has been associated with the induction of Fas response (31 -33), activation of c-Jun (22, 34 -36), and induction of the apoptotic cascade by mitochondria destabilization (1,37,38).…”

Section: Introductionmentioning

confidence: 99%

RRR-α-Tocopherol succinate down-regulates oncogenic Ras signaling

Donapaty

Louis

Horvath

et al. 2006

Molecular Cancer Therapeutics

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A-Tocopherol succinate (TS), an analogue of vitamin E, has growth-inhibitory activity in a wide spectrum of in vitro and in vivo cancer models. Here, we report that modulation of oncogenic Ras is associated with TS activity. TS inhibits the proliferation and induces apoptosis of NIH3T3 cells stably transfected with oncogenic K-Ras and H-Ras, but not NIH3T3 cells expressing empty vector. TS treatment resulted in decreased Ras protein levels in oncogenic Ras expressing NIH3T3 cells but not in parental NIH3T3 cells. Treatment with TS suppressed the levels of phospho-Akt and phospho-Erk1/2 in oncogenic Ras expressing NIH3T3 cells. Overexpression of constitutively active phosphoinositide-3-kinase, Akt, and Mek1/2 significantly attenuated TS growth inhibition of oncogenic Ras-transformed NIH3T3 mouse fibroblast cell lines. In addition, transcriptional targets of oncogenic Ras such as c-Myc, cyclin D1, and E2F1 were down-regulated by TS in oncogenic Ras-expressing cells. The above TS effects on oncogenic Ras signaling were also observed in endogenous oncogenic K-Ras expressing HCT 116 (human colon cancer) and MDA-MB-231 (human breast cancer) cells. Taken together, these data show that TS down-regulation of the Ras signaling pathways that are mediated by Mek/Erk and phosphoinositide-3-kinase/Akt plays, at least in part, a critical role in TS inhibition of proliferation and survival of transformed cells. This data supports further investigation of the chemopreventive and therapeutic potential of TS in tumors that are dependent on activated Ras signaling and identifies phosphor-Erk and phosphor-Akt as potential biomarkers of TS activity.

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RRR‐α‐tocopheryl succinate enhances TGF‐β₁, ‐β₂, and ‐β₃and TGF‐βR‐II expression by human MDA‐MB‐435 breast cancer cells

Cited by 29 publications

References 44 publications

RRR-α-tocopheryl succinate induction of prolonged activation of c-jun amino-terminal kinase and c-jun during induction of apoptosis in human MDA-MB-435 breast cancer cells

RRR-α-tocopheryl succinate induction of prolonged activation of c-jun amino-terminal kinase and c-jun during induction of apoptosis in human MDA-MB-435 breast cancer cells

Inhibition of lung carcinoma cell growth by high density lipoprotein-associated ?-tocopheryl-succinate

RRR-α-Tocopherol succinate down-regulates oncogenic Ras signaling

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