Inhibition of proliferation and induction of apoptosis by γ-tocotrienol in human colon carcinoma HT-29 cells

Xu, Weili; Liu, Jiaren; Liu, Huikun; Qi, Guiyun; Sun, Xiangrong; Sun, Weizheng; Chen, Bingqing

doi:10.1016/j.nut.2008.10.019

Cited by 80 publications

(66 citation statements)

References 53 publications

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“…T3 has been shown to mediate its activity against a variety of chronic diseases, including cardiovascular diseases, neurologic diseases, diabetes, and cancer (9)(10)(11)(12)(13)(14). T3s have shown anticancer activity against cancers such as colon, breast, liver, lung, kidney, prostate, skin, and other cancers both in vitro (15)(16)(17)(18)(19)(20) and in vivo (21)(22)(23)(24)(25). T3 has the potency to induce apoptosis in a variety of cancer cell types (types 1-5).…”

Section: Introductionmentioning

confidence: 99%

γ-Tocotrienol Promotes TRAIL-Induced Apoptosis through Reactive Oxygen Species/Extracellular Signal-Regulated Kinase/p53–Mediated Upregulation of Death Receptors

Kannappan

Ravindran

Prasad

et al. 2010

Molecular Cancer Therapeutics

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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor superfamily, is in clinical trials for cancer therapy, but its anticancer potential is limited by the development of resistance. We investigated the ability of tocotrienol (T3), an unsaturated vitamin E present in palm oil, rice bran, barley, oats, and wheat germ, to sensitize tumor cells to TRAIL. Results from esterase staining, colony formation, caspase activation, and sub-G 1 cell cycle arrest revealed that γ-T3 can sensitize human colon cancer cells to TRAIL. When examined for the mechanism, we found that γ-T3 significantly downregulated the expression of antiapoptotic proteins (c-IAP2 and Bcl-xL). We also found that γ-T3, but not tocopherol, induced the expression of the TRAIL receptors death receptor (DR)-4 and DR5. This induction was not cell type specific, as upregulation was also found in pancreatic, kidney, and leukemic cells. Upregulation of DRs by γ-T3 required the production of reactive oxygen species (ROS), and sequestering of ROS abolished both upregulation of the receptors and potentiation of TRAIL-induced apoptosis. Induction of DRs by γ-T3 also required activation of extracellular signal-regulated kinase 1 (ERK1), as silencing of ERK1 by specific siRNA abrogated the upregulation of TRAIL receptors. Further, induction of DRs by γ-T3 required the expression of p53 and Bax, as no induction of the receptors was found in colon cancer cells with deletion of these genes. Overall, our results show that γ-T3 sensitizes tumor cells to TRAIL by upregulating DRs through the ROS/ ERK/p53 pathway and by downregulating cell survival proteins. Mol Cancer Ther; 9(8); 2196-207. ©2010 AACR.

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Section: Introductionmentioning

confidence: 99%

γ-Tocotrienol Promotes TRAIL-Induced Apoptosis through Reactive Oxygen Species/Extracellular Signal-Regulated Kinase/p53–Mediated Upregulation of Death Receptors

Kannappan

Ravindran

Prasad

et al. 2010

Molecular Cancer Therapeutics

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“…35 The anticancer effect of T3 was found to be mediated through antiproliferation, 16,36,37 induction of apoptosis, 38,39 cell cycle arrest, 13,40 antiangiogenesis 41 and antiinvasion. 18 More recently, c-T3, one of the four isoforms of T3, was reported to possess chemosensitizing effects, 17,18 which led us to speculate that c-T3 may be able to target the chemoresistant cancer stem-like cells.…”

Section: Discussionmentioning

confidence: 99%

“…Increasing evidence suggests that T3s possess substantial anticancer effects in many types of cancers, including breast, liver, lung, gastric, colon, skin and prostate cancer. [11][12][13][14][15][16][17] Recently, we have reported that among the four isoforms (a, b, c and d) of T3, the gamma isoform (c-T3) possesses the most potent anticancer effect against prostate cancer cells. 18 By comparing the effect of the four T3 isomers on nonmalignant prostate epithelial cells and prostate cancer cell lines, we found that c-T3 is more effective in inhibiting both the growth and survival of prostate cancer cells.…”

mentioning

confidence: 99%

Gamma‐tocotrienol as an effective agent in targeting prostate cancer stem cell‐like population

Luk

Yap²,

Chiu

et al. 2011

Intl Journal of Cancer

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Emerging evidence supports that prostate cancer originates from a rare subpopulation of cells, namely prostate cancer stem cells (CSCs). Conventional therapies for prostate cancer are believed to mainly target the majority of differentiated tumor cells but spare CSCs, which may account for the subsequent disease relapse after treatment. Therefore, successful elimination of CSCs may be an effective strategy to achieve complete remission from this disease. Gamma‐tocotrienols (γ‐T3) is one of the vitamin‐E constituents, which have been shown to have anticancer effects against a wide range of human cancers. Recently, we have reported that γ‐T3 treatment not only inhibits prostate cancer cell invasion but also sensitizes the cells to docetaxel‐induced apoptosis, suggesting that γ‐T3 may be an effective therapeutic agent against advanced stage prostate cancer. Here, we demonstrate for the first time that γ‐T3 can downregulate the expression of prostate CSC markers (CD133/CD44) in androgen‐independent prostate cancer cell lines (PC‐3 and DU145), as evident from Western blotting analysis. Meanwhile, the spheroid formation ability of the prostate cancer cells was significantly hampered by γ‐T3 treatment. In addition, pretreatment of PC‐3 cells with γ‐T3 was found to suppress tumor initiation ability of the cells. More importantly, although CD133‐enriched PC‐3 cells were highly resistant to docetaxel treatment, these cells were as sensitive to γ‐T3 treatment as the CD133‐depleted population. Our data suggest that γ‐T3 may be an effective agent in targeting prostate CSCs, which may account for its anticancer and chemosensitizing effects reported in previous studies.

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“…It has been well documented that the combination of gambogic acid and celastrol has a synergistic antitumor effect. The effect can be attributed to apoptosis induced by a decrease in NF-κB pathway activation, therefore, NF-κB p65 protein may be involved (26,27). The inhibition of NF-κB augments sensitivity to 5-FU/folinic acid in colon cancer (28).…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA potentiates the efficacy of 5-FU in Colo205 colon cancer cells in vivo through downregulation of P-gp and LC3-II

2011

Experimental and Therapeutic Medicine

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Abstract. Traditional Chinese herbal medicines are widely accepted as an option for the treatment of colorectal cancers. Danshen (Salviae miltiorrhizae Radix) is widely prescribed in traditional Chinese medicine for cardiovascular diseases. Tanshinone IIA (Tan-IIA) is extracted from Danshen. Our previous studies have shown that Tan-IIA induces apoptosis in Colo205 human colon cancer cells in vitro and in vivo. In the present study, we investigated the efficacy of Tan-IIA and 5-fluorouracil (5-FU) in a Colo205 cell xenograft model. For in vivo studies, SCID mice were engrafted with Colo205 cells and from day 10 onwards were randomly divided into 3 groups and treated with 5-FU plus Tan-IIA, 5-FU plus corn oil, and the vehicle alone. At the end of a 4-week dosing schedule, the SCID mice were sacrificed and xenograft tumors were dissected for protein western blot analysis. Our results showed that the Colo205 xenograft model co-treated with Tan-IIA plus 5-FU caused a reduction in the xenograft tumor volumes and decreased P-glycoprotein (P-gp) and microtubule-associated protein light chain 3 (LC3)-II expression compared to 5-FU alone. Based on these observations, it may be possible to develop Tan-IIA plus 5-FU as therapeutic agents for human colon cancer.

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Inhibition of proliferation and induction of apoptosis by γ-tocotrienol in human colon carcinoma HT-29 cells

Cited by 80 publications

References 53 publications

γ-Tocotrienol Promotes TRAIL-Induced Apoptosis through Reactive Oxygen Species/Extracellular Signal-Regulated Kinase/p53–Mediated Upregulation of Death Receptors

γ-Tocotrienol Promotes TRAIL-Induced Apoptosis through Reactive Oxygen Species/Extracellular Signal-Regulated Kinase/p53–Mediated Upregulation of Death Receptors

Gamma‐tocotrienol as an effective agent in targeting prostate cancer stem cell‐like population

Tanshinone IIA potentiates the efficacy of 5-FU in Colo205 colon cancer cells in vivo through downregulation of P-gp and LC3-II

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