Trans10, cis12-conjugated linoleic acid induces mitochondria-related apoptosis and lysosomal destabilization in rat hepatoma cells

Yamasaki, Masao; Miyamoto, Yumi; Chujo, Hitomi; Nishiyama, Kazuo; Tachibana, Hirofumi; Yamada, Koji

doi:10.1016/j.bbalip.2005.05.010

Cited by 25 publications

(19 citation statements)

References 26 publications

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“…This demonstrates activation of the intrinsic mitochondrial apoptotic pathway, an effect that was time-and concentrationdependent. Our data confirm and extend previous studies in colon cancer and hepatoma cells which reported that this isomer stimulated the activities of caspases-3 and -9 [23,24] and release of cytochrome c into the cytosol [23,25]. Importantly, our studies point to a critical role for Bcl-2 in mediating the apoptotic effects of CLA in TM4t cells.…”

Section: Discussionsupporting

confidence: 92%

“…Truncated Bid (tBid), a known amplifier of the mitochondrial apoptotic pathway [30], may collaborate in CLA-induced apoptosis, since we found that caspase-8, the enzyme responsible for the proteolytic cleavage of Bid to tBid, was activated by t10,c12-CLA in TM4t cells in a time-and concentration-dependent manner (data not shown). In support of this theory, Yamasaki et al [25] reported that full length Bid was decreased in t10,c12-CLA-treated hepatoma cells, although this group did not show whether tBid was increased concurrently.…”

Section: Discussionmentioning

confidence: 97%

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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: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 97%

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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“…Bcl2 was also upregulated in the DHA and C18:3n-3 48h treatments but after 72h of treatment, only the DHA treated cells still showed significant stimulation. The relationship between ROS and apoptosis is commonly found among many system studying the effect of novel drugs including cholesterol statins and omega-3 fatty acids [13]. In these trials, these fatty acids also showed a significant effect on expression but the amount of expression was quite variable, even after 4 separate trials.…”

Section: Discussionmentioning

confidence: 99%

“…In response to ROS, a cascade of genes may be activated to either deal with detoxification to prevent potentially damaging effects of ROS or to call out for assistance by the inflammasome [12]. Too much inflammation will also result in damage, leading to apoptosis activation, necrosis and cell death [13]. Similar mechanism dealing with oxidative stress has been speculated to occur with the omega-3 fatty acid, C18:3n-3 (α-linolenic acid) and to a much greater effect by the long chain omega-3 fatty acids C20:5n-3 eicosapentaenoic acid (EPA) and C22:6n-3 docosahexaenoic acid (DHA) [14,15].…”

Section: Introductionmentioning

confidence: 99%

CLA isomer t10,c12 induce oxidation and apoptosis in 3t3 adipocyte cells in a similar effect as omega-3 linolenic acid and DHA.

Meadus¹,

Vahmani²,

Duff³

et al. 2017

FFHD

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Citation: Meadus WJ, Vahmani P, Duff P, Zantinge JL, Turner TD, and Dugan M.E.R. Oxidation and apoptosis are induced by CLA-t10c12 similar to DHA in 3T3 adipocyte cells. Functional Foods in Health and Disease 2017; 7(2): 149-167 ABSTRACT Background: Commercial conjugated linoleic acid (CLA) dietary supplements contain an equal mixture of the C18:2 isomers, cis-9trans-11 and trans-10cis-12. Predominantly, CLAc9t11 occurs naturally in meat and dairy products at ~ 0.5% of total fat , whereas CLAt10c12 occurs at > 0.1%. Recent studies show that CLA-c9t11 generally promotes lipid accumulation but CLA-t10c12 may inhibit lipid accumulation and may also promote inflammation. The omega-3 fatty acids α-linolenic acid (C18:3n-3) and docosahexaenoic acid (DHA) have also been observed to inhibit lipid accumulation and effect inflammation; therefore we examined the effects of the two main isomers of CLA and omega -3 fatty acids C18:3n-3 and DHA at the molecular level to determine if they are causing similar oxidative stresses.Methods: Purified CLA-c9t11 and CLA-t10c12 were added to 3T3 cells induced into mature adipocyte cultures at 100uM concentrations and compared with 100uM C18:3n-3 (α-linolenic acid) and 50uM docosahexaenoic acid (DHA) to observe their effect on growth, gene transcription and general oxidation. The results of multiple separate trials were averaged and compared for significance at levels of P < 0.05, using one way ANOVA and Student's t-test.Results: C18:3n-3, DHA and CLA-t10c12 inhibited 3T3 adipose cell growth and caused a significant increase in lipid hydro peroxide activity. CLA-t10c12 and c9t11 increased AFABP, FAS and ACOX1 mRNA gene expression but DHA and C18:3n-3 decreased the same mRNAs. CLA-c9t11 but not the t10c12 stimulated adipoQ expression even though; CLA-c9t11 had only a slightly greater affinity for PPARγ than CLA-t10c12, according to TR-FRET assays. The expression of the xenobiotic metabolism genes, aldo-keto reductase 1c1 (akr1c1), superoxide dismutase (SOD) and inflammation chemokine secretions of eotaxin (CCL11), Rantes (CCL5), MIG (CCL9) and MCP-1 were increased by DHA, C18:3n-3 and CLA-t10c12 but not CLA-c9t11. This correlated with an increase in apoptosis factors, caspase 3, Bcl-2 and BAXs. Apoptosis factors were partially reduced by co-treatment with lipophilic anti-oxidant α-tocopherol.Conclusions: CLA-t10c12 stimulated the production of more reactive oxygen species (ROS) than CLA-c9t11. In response, cascades of genes are activated in detoxification, inflammation or apoptosis, to deal with the potentially damaging effects of ROS including CCL5 and MCP-1. This was similar to treatment with the omega-3 fatty acids but the fat metabolic enzymes were generally inhibited by C18:3n-3 and DHA except CLA-t10c12 which did not stimulate adipoQ.

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“…In particular, t10, c12-CLA appears to be effective against some cancer cell lines and obesity. For instance, we previously reported that t10, c12-CLA showed potent cytotoxic effect on liver cancer cells in vitro 7,8 . However, t10, c12-CLA tends to be rapidly metabolized and thus cleared from the blood stream 9,10 .…”

Section: Introductionmentioning

confidence: 99%

Preparation of Conjugated Linoleic Acid Microemulsions and their Biodistribution

et al. 2016

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Trans10, cis12-conjugated linoleic acid induces mitochondria-related apoptosis and lysosomal destabilization in rat hepatoma cells

Cited by 25 publications

References 26 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

CLA isomer t10,c12 induce oxidation and apoptosis in 3t3 adipocyte cells in a similar effect as omega-3 linolenic acid and DHA.

Preparation of Conjugated Linoleic Acid Microemulsions and their Biodistribution

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