The antiproliferative effects of biologically active isomers of conjugated linoleic acid on human colorectal and prostatic cancer cells

Molecular Medicine Reports

et al. 2015

Abstract. Khz (fusion of Ganoderma lucidum and Polyporus umbellatus), isolated from the mycelia of G. lucidum and P. umbellatus, exerts anti-proliferative effects against malignant cells; however, its activity against human breast cancer cells remains to be elucidated. In the present study, cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and poptosis was examined using annexin V-propidium iodide staining and flow cytometry. The activation of caspases 7, 8 and 9 were detected in the Khz-treated cells using western blotting. The results demonstrated that Khz increased the intracellular calcium concentration and induced the production of reactive oxygen species in MCF-7 breast cancer cells, as determined using flow cytometry. The results also demonstrated that Khz inhibited cell proliferation and induced apoptosis in the MCF-7 cells. In addition, the mechanism by which Khz induces apoptosis in cancer cells was investigated. Khz induced apoptosis preferentially in transformed cells, with a minimal effect on non-transformed cells, suggesting its potential as an anticancer therapeutic agent. Oxidative stress is associated with apoptotic and non-apoptotic cell death, although pro-oxidative conditions are not a pre-requisite for apoptosis. Assessment of the activation status of caspases 7, 8 and 9 revealed that the levels of cleaved caspases were significantly increased in the cells treated with Khz. It is widely accepted that calcium signaling is important in apoptosis, and the present study observed an increase in [Ca 2+ ] i in response to Khz treatment. The anti-proliferative and pro-apoptotic effects of Khz suggest that this extract may be developed as a potential anticancer agent.

Section: Methodsmentioning

confidence: 99%

Induction of apoptosis in MCF-7 human breast cancer cells by Khz (fusion of Ganoderma lucidum and Polyporus umbellatus mycelium)

Molecular Medicine Reports

et al. 2015

“…CLA has been shown to have many potential health benefits, such as lean body mass deposition (2) , antidiabetes (3) , antiinflammation (4) , anticarcinogenesis (5) and anti-atherogenesis effects (6) . CLA can stimulate or inhibit immune cell function, and among CLA isomers, trans-10, cis-12 (t10c12)-CLA has shown to participate in the modulation of pro-or anti-inflammatory cytokine secretion (7) .…”

mentioning

confidence: 99%

Trans-10,cis-12-conjugated linoleic acid modulates NF-κB activation and TNF-α production in porcine peripheral blood mononuclear cells via a PPARγ-dependent pathway

Kang

et al. 2010

Br J Nutr

The activation of PPARg by ligands, including conjugated linoleic acid (CLA) isomers, plays an important role in the immune response. Among CLA isomers, trans-10, cis-12 (t10c12)-CLA is known to participate in the modulation of pro-inflammatory cytokine secretion. The aim of the present study was to assess the effect of t10c12-CLA on PPARg activation, NF-kB activation and TNF-a expression in lipopolysaccharide (LPS)-naive and LPS-stimulated porcine peripheral blood mononuclear cells (PBMC). In addition, the effect of PPARg inhibition on NF-kB activation and TNF-a expression in porcine PBMC was examined. t10c12-CLA was found to increase TNF-a expression and NF-kB activity in LPS-naive porcine PBMC. In contrast, t10c12-CLA decreased TNF-a expression and NF-kB activity in LPS-stimulated porcine PBMC. t10c12-CLA up-regulated PPARg activity and mRNA expression in both LPS-naive and LPS-stimulated porcine PBMC. GW9662, a PPARg antagonist, completely negated the modulating effects of t10c12-CLA on TNF-a expression and NF-kB activity in both LPS-naive and LPS-stimulated porcine PBMC. These results suggest that t10c12-CLA can modulate TNF-a production and NF-kB activation by a PPARg-dependent pathway in porcine PBMC.

“…We (37) have previously shown that dietary CLA inhibits the development of colon tumors in rats treated with 1,2-dimethylhydrazine. In vitro studies also have shown that CLA inhibits the growth of SW480 (34) and HT-29 cells (35,42), the human colon cancer lines. The present study indicates that CLA inhibits HT-29 cell growth by both decreasing cell proliferation and inducing apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…We (37) previously reported that dietary CLA inhibited colon cancer incidence in rats treated with 1,2-dimethylhydrazine. In addition to animal studies, in vitro studies have shown that CLA inhibits the growth of the human colon cancer cells, SW480 (34) and HT-29 (35,42). Strong evidence for the anticancer abilities of CLA indicates a need to study the mechanisms of chemoprotection by CLA.…”

mentioning

confidence: 99%

Conjugated linoleic acid inhibits cell proliferation and ErbB3 signaling in HT-29 human colon cell line

Cho¹,

American Journal of Physiology-Gastrointestinal and Liver Physi

Kim³

et al. 2003

115

Conjugated linoleic acid (CLA) has chemoprotective properties in experimental cancer models, and in vitro studies have shown that CLA inhibits HT-29 colon cancer cell growth. ErbB2 and ErbB3 have been implicated in the development of colon cancer, and both proteins are expressed at high levels in the HT-29 cell line. Activation of ErbB2/ErbB3 heterodimers is regulated by the ErbB3 ligand heregulin. To examine CLA regulation of HT-29 cell proliferation and apoptosis and the influence of CLA on the ErbB3 signaling pathway, HT-29 cells were cultured in the presence of CLA and/or heregulin. CLA inhibited DNA synthesis and induced apoptosis of HT-29 cells. Although the addition of heregulin-␣ led to an increase in cell number, it was not able to counteract the negative growth regulatory effect of CLA. Immunoprecipitation/Western blot studies revealed that CLA inhibited heregulin-␣-stimulated phosphorylation of ErbB2 and ErbB3, recruitment of the p85 subunit of phosphoinositide 3-kinase (PI3-kinase) to the ErbB3 receptor, ErbB3-associated PI3-kinase activities, and phosphorylation of Akt. CLA decreased ErbB2 and ErbB3 mRNA and protein levels in a dose-dependent manner. In conclusion, we demonstrate that CLA inhibits cell proliferation and stimulates apoptosis in HT-29 cells and that this may be mediated by its ability to downregulate ErbB3 signaling and the PI3-kinase/Akt pathway.