Conjugated linoleic acids (CLAs) regulate the expression of key apoptotic genes in human breast cancer cells

Majumder, Barun; Wahle, Klaus W.J.; Moir, Susanne; Schofield, Andrew Craig; Choe, Sun-Nam; Farquharson, Andrew J.; Grant, I. S.; Heys, Steven Darryll

doi:10.1096/fj.01-0720fje

Cited by 89 publications

(52 citation statements)

References 31 publications

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“…Importantly, our studies point to a critical role for Bcl-2 in mediating the apoptotic effects of CLA in TM4t cells. Previous Western blot studies indicated that t10,c12-CLA induced either a modest 20-25% loss, or no loss, of total cellular Bcl-2 protein in cultured colon, prostate or breast cancer cells [23,26,27]. However, using mitochondrial fractions, we found that t10,c12-CLA induced a marked concentrationdependent decrease of mitochondrial Bcl-2 after 3 days of treatment (10% of control levels relative to VDAC at 40 μM).…”

Section: Discussioncontrasting

confidence: 49%

Conjugated linoleic acid induces apoptosis of murine mammary tumor cells via Bcl-2 loss

Lisafeld

et al. 2007

Biochemical and Biophysical Research Communications

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Conjugated linoleic acid (CLA) is a powerful anticancer agent in a number of tumor model systems; however, its precise mechanism of action remains elusive. Here, we report that t10,c12 CLA, a component of synthetic CLA supplements, induced apoptosis and G 1 arrest of p53 mutant TM4t murine mammary tumor cells. Furthermore, t10,c12-CLA induced a time-and concentrationdependent cleavage of caspases-3 and -9, and release of cytochrome c from mitochondria to cytosol. Levels of Bcl-2 protein were decreased both in total cellular lysates and in mitochondria after t10,c12-CLA treatment; however, there was no significant change in Bax or Bak. Overexpression of Bcl-2 attenuated apoptosis in response to t10,c12-CLA treatment. These results demonstrate that t10,c12-CLA triggers apoptosis of p53 mutant murine mammary tumor cells through the mitochondrial pathway by targeting Bcl-2.

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Section: Discussioncontrasting

confidence: 49%

Conjugated linoleic acid induces apoptosis of murine mammary tumor cells via Bcl-2 loss

Lisafeld

et al. 2007

Biochemical and Biophysical Research Communications

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“…We also examined the effect of linoleic acid and conjugated linoleic acid on the proliferation of MCF-10A cells. Because Majumder et al (15) reported that conjugated linoleic acid could inhibit the proliferation of MCF-10A, a dose-response experiment was done. We found that under our cell culture conditions, the proliferation of MCF-10A cells was only slightly affected by either linoleic acid or conjugated linoleic acid.…”

Section: Resultsmentioning

confidence: 99%

Anti-Aromatase Activity of Phytochemicals in White Button Mushrooms (Agaricus bisporus)

et al. 2006

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White button mushrooms (Agaricus bisporous) are a potential breast cancer chemopreventive agent, as they suppress aromatase activity and estrogen biosynthesis. Therefore, we evaluated the activity of mushroom extracts in the estrogen receptor-positive/aromatase-positive MCF-7aro cell line in vitro and in vivo. Mushroom extract decreased testosterone-induced cell proliferation in MCF-7aro cells but had no effect on MCF-10A, a nontumorigenic cell line. Most potent mushroom chemicals are soluble in ethyl acetate. The major active compounds found in the ethyl acetate fraction are unsaturated fatty acids such as linoleic acid, linolenic acid, and conjugated linoleic acid. The interaction of linoleic acid and conjugated linoleic acid with aromatase mutants expressed in Chinese hamster ovary cells showed that these fatty acids inhibit aromatase with similar potency and that mutations at the active site regions affect its interaction with these two fatty acids. Whereas these results suggest that these two compounds bind to the active site of aromatase, the inhibition kinetic analysis indicates that they are noncompetitive inhibitors with respect to androstenedione. Because only conjugated linoleic acid was found to inhibit the testosteronedependent proliferation of MCF-7aro cells, the physiologically relevant aromatase inhibitors in mushrooms are most likely conjugated linoleic acid and its derivatives. The in vivo action of mushroom chemicals was shown using nude mice injected with MCF-7aro cells. The studies showed that mushroom extract decreased both tumor cell proliferation and tumor weight with no effect on rate of apoptosis. Therefore, our studies illustrate the anticancer activity in vitro and in vivo of mushroom extract and its major fatty acid constituents.

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“…MCF-10A cells have intact cell cycle checkpoint controls (33 -38), are aneuploid but have stable genomes comparable with human mammary epithelial cells (36), and have normal proliferation controls, including contact inhibition (31, 39 -43) and normal apoptotic machinery (37,38,44,45).…”

Section: Methodsmentioning

confidence: 99%

Docetaxel induces cell death through mitotic catastrophe in human breast cancer cells

Morse¹,

Gray

Payne

et al. 2005

Molecular Cancer Therapeutics

248

196

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Apoptosis has long been considered to be the prevailing mechanism of cell death in response to chemotherapy. Currently, a more heterogeneous model of tumor response to therapy is acknowledged wherein multiple modes of death combine to generate the overall tumor response. The resulting mechanisms of cell death are likely determined by the mechanism of action of the drug, the dosing regimen used, and the genetic background of the cells within the tumor. This study describes a nonapoptotic response to docetaxel therapy in human breast cancer cells of increasing cancer progression (MCF-10A, MCF-7, and MDA-mb-231). Docetaxel is a microtubule-stabilizing taxane that is being used in the clinic for the treatment of breast and prostate cancers and small cell carcinoma of the lung. The genetic backgrounds of these cells were characterized for the status of key pathways and gene products involved in drug response and cell death. Cellular responses to docetaxel were assessed by characterizing cell viability, cell cycle checkpoint arrest, and mechanisms of cell death. Mechanisms of cell death were determined by Annexin V binding and scoring of cytology-stained cells by morphology and transmission electron microscopy. The primary mechanism of death was determined to be mitotic catastrophe by scoring of micronucleated cells and cells undergoing aberrant mitosis. Other, nonapoptotic modes of death were also determined. No significant changes in levels of apoptosis were observed in response to docetaxel. [Mol Cancer Ther 2005;4(10):1495 -504]

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Conjugated linoleic acids (CLAs) regulate the expression of key apoptotic genes in human breast cancer cells

Cited by 89 publications

References 31 publications

Conjugated linoleic acid induces apoptosis of murine mammary tumor cells via Bcl-2 loss

Conjugated linoleic acid induces apoptosis of murine mammary tumor cells via Bcl-2 loss

Anti-Aromatase Activity of Phytochemicals in White Button Mushrooms (Agaricus bisporus)

Docetaxel induces cell death through mitotic catastrophe in human breast cancer cells

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