Conjugated linoleic acid induces apoptosis in MDA-MB-231 breast cancer cells through ERK/MAPK signalling and mitochondrial pathway

Miglietta, Antonella; Bozzo, Francesca; Bocca, Claudia; Gabriel, Ludovica; Trombetta, Antonella; Belotti, S; Canuto, Rosa Angela

doi:10.1016/j.canlet.2005.03.029

Cited by 67 publications

(43 citation statements)

References 28 publications

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“…1A). Prior work with MDA-MB-231 cells with CLA at higher doses found there was a significant reduction in proliferation (14); however, another study using a variety of cell lines (DLD-1, Hep G 2 , A549, MCF-7, and MKN-7) reported that at the lower concentrations such as what we used, there was negligible inhibition of proliferation (15). MDA-wt and MDA-ERα7 cells had similar levels of inhibition that were not statistically different, illustrating that ERα was not involved in the effects of α-ESA.…”

Section: Ability Of α-Esa To Inhibit Breast Cancer Growth and Induce mentioning

confidence: 90%

Eleostearic Acid Inhibits Breast Cancer Proliferation by Means of an Oxidation-Dependent Mechanism

Großmann

Mizuno

Dammen

et al. 2009

Cancer Prevention Research

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Eleostearic acid (α-ESA) is a conjugated linolenic acid that makes up ∼60% of Momordica charantia (bitter melon) seed oil. Prior work found that water extract from bitter melon was able to inhibit breast cancer. Here, we investigated effects of α-ESA on both estrogen receptor (ER)-negative MDA-MB-231 (MDA-wt) and ER-positive MDA-ERα7 human breast cancer cells. We found that α-ESA inhibited proliferation of both MDA-wt and MDA-ERα7 cells, whereas conjugated linoleic acid had comparatively weak antiproliferative activity at 20 to 80 μmol/L concentrations. We also found that α-ESA (40 μmol/L) treatment led to apoptosis in the range of 70% to 90% for both cell lines, whereas conjugated linoleic acid (40 μmol/L) resulted in only 5% to 10% apoptosis, similar to results for control untreated cells. Addition of α-ESA also caused loss of mitochondrial membrane potential and translocation of apoptosis-inducing factor as well as endonuclease G from the mitochondria to the nucleus. Additionally, α-ESA caused a G 2 -M block in the cell cycle. We also investigated the potential for lipid peroxidation to play a role in the inhibitory action of α-ESA. We found that when the breast cancer cells were treated with α-ESA in the presence of the antioxidant α-tocotrienol (20 μmol/L), the growth inhibition and apoptosis effects of α-ESA were lost. An AMP-activated protein kinase inhibitor (Dorsomorphin) was also able to partially abrogate the effects of α-ESA, whereas a caspase inhibitor (BOC-D-FMK) did not. These results illustrate that α-ESA can block breast cancer cell proliferation and induce apoptosis through a mechanism that may be oxidation dependent.

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Section: Ability Of α-Esa To Inhibit Breast Cancer Growth and Induce mentioning

confidence: 90%

Eleostearic Acid Inhibits Breast Cancer Proliferation by Means of an Oxidation-Dependent Mechanism

Großmann

Mizuno

Dammen

et al. 2009

Cancer Prevention Research

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“…[9][10][11][12] In previous studies, we have reported that CLA inhibits the growth of different human cancer cell lines, among which are breast cancer cells. 13 CLA's suppression of cell proliferation was in some cases positively correlated with inhibition of mitogen-activated protein kinase/extracellular signal-related kinase, 14,15 but the underlying mechanisms by which CLA interfered with cell proliferation have not been fully clarified. Interestingly, it has been recently reported that CLA could modulate lipid metabolism, cellular proliferation and differentiation through the activation of peroxisome proliferator-activated receptors (PPARs).…”

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confidence: 99%

Involvement of PPARγ and E‐cadherin/β‐catenin pathway in the antiproliferative effect of conjugated linoleic acid in MCF‐7 cells

Bocca

Bozzo

Francica

et al. 2007

Intl Journal of Cancer

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Conjugated linoleic acid (CLA) is a naturally occurring fatty acid, which has been shown to exert beneficial effects against breast carcinogenesis. It has been reported that CLA could modulate cellular proliferation and differentiation through the activation of peroxisome proliferator-activated receptors (PPARs). Among different PPAR isotypes, PPARc is involved in growth inhibition of transformed cells. Ligands of PPARc are considered as potential anticancer drugs, so CLA was tested for its ability to induce PPARc expression in MCF-7 breast cancer cells. The effects of CLA and of a specific synthetic PPARc antagonist were evaluated on cell growth as well as on parameters responsible for cell growth regulation. We demonstrated here that CLA stimulated the expression of PPARc to levels up to control and caused PPARc translocation into the nucleus. Furthermore, the overexpression of PPARc positively correlates with the inhibition of cell proliferation and with the modulation of ERK signaling induced by CLA; in all cases the administration of the antagonist reverted CLA effects. The PPAR-signaling pathway is connected with the b-catenin/Ecadherin pathway, thus we evaluated CLA effects on the expression and cellular distribution of these proteins, which are involved in cell adhesion and responsible for invasive behavior. The treatment with CLA determined the up-regulation and the redistribution of b-catenin and E-cadherin and the antagonist reverted only the effect on b-catenin. These studies indicate that CLA regulates PPARc expression by selectively acting as an agonist and may influence cell-cell adhesion and invasiveness of MCF-7 cells. ' 2007 Wiley-Liss, Inc.

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“…3 The majority of animal studies have concerned breast, colon and prostate tumors. 4 CLA has been found to inhibit cell proliferation or induce cell death in human tumor cell lines [5][6][7][8][9] ; among these, hepatoma cell lines have been demonstrated to be affected by CLA, with inhibition of cell proliferation or induction of apoptosis depending on the degree of deviation. 7 Despite considerable work having been done to demonstrate the importance of CLA as an anticancer agent, the mechanisms mediating its effects are not fully understood.…”

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confidence: 99%

PPARα and PP2A are involved in the proapoptotic effect of conjugated linoleic acid on human hepatoma cell line SK‐HEP‐1

Muzio

Maggiora

Oraldi

et al. 2007

Intl Journal of Cancer

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Conjugated linoleic acid (CLA), found in dairy products, in beef and lamb has been demonstrated to possess anticancer properties protecting several tissues from developing cancer. Moreover, it has been shown to modulate apoptosis in several cancer cell lines. The aim of this study was to investigate which signaling transduction pathways were modulated in CLA‐induced apoptosis in human hepatoma SK‐HEP‐1 cells. The cells exposed to CLA were evaluated for PPARα, PP2A, pro‐apoptotic proteins Bak, Bad and caspases, and anti‐apoptotic proteins Bcl‐2 and Bcl‐XL. Cells were also treated with okadaic acid, a PP2A inhibitor, or with Wy‐14643, a specific PPARα agonist. The CLA‐induced apoptosis was concomitant to the increase of percentage of cells in the S phase, PPARα, PP2A and pro‐apoptotic proteins; simultaneously, antiapoptotic proteins decreased. Inhibition of PP2A prevented apoptosis, and PPARα agonist showed similar effect as CLA. The increased PP2A could be responsible for the dephosphorylation of Bcl‐2 and Bad, permitting apoptotic activity of Bax and Bad. The increase of caspase 8 and 9 suggested that both the intrinsic and extrinsic apoptotic pathways were induced. PP2A was probably increased by PPARα, since putative PPRE sequences were found in genes encoding its subunits. In conclusion, CLA induces apoptosis in human hepatoma SK‐HEP‐1 cells, by increasing PPARα, PP2A and pro‐apoptotic proteins. © 2007 Wiley‐Liss, Inc.

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Conjugated linoleic acid induces apoptosis in MDA-MB-231 breast cancer cells through ERK/MAPK signalling and mitochondrial pathway

Cited by 67 publications

References 28 publications

Eleostearic Acid Inhibits Breast Cancer Proliferation by Means of an Oxidation-Dependent Mechanism

Eleostearic Acid Inhibits Breast Cancer Proliferation by Means of an Oxidation-Dependent Mechanism

Involvement of PPARγ and E‐cadherin/β‐catenin pathway in the antiproliferative effect of conjugated linoleic acid in MCF‐7 cells

PPARα and PP2A are involved in the proapoptotic effect of conjugated linoleic acid on human hepatoma cell line SK‐HEP‐1

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