The natural antioxidant alpha-lipoic acid induces p27Kip1-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells

Dozio, Elena; Ruscica, Massimiliano; Passafaro, Luca; Dogliotti, Giada; Steffani, Liliana; Pagani, Alessandra Almeida Castro; Demartini, G.; Esposti, D.; Fraschini, F.; Magni, Paolo

doi:10.1016/j.ejphar.2010.05.009

Cited by 88 publications

(69 citation statements)

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“…Perhaps the cancer cell death observed with the LACPEG micelles is not an indicator of toxicity but instead an observation of the carrier's apoptotic potential towards cancer cell lines. For instance, its lipoic acid component, has been shown to inhibit cell proliferation and growth, as well as induce the selective apoptosis of a number of cancer cell lines (through the downregulation of the BCL-2 protein), including lung cancer cells (Choi et al, 2009;Dozio et al, 2010;Michikoshi et al, 2013;Moungjaroen et al, 2006;Na et al, 2009;Wenzel et al, 2005). Furthermore, previous studies have also shown that chitosan inhibits cell proliferation and metastases, as well as induces apoptosis (Hasegawa et al, 2001;Kim et al, 2013).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…growth (by inhibiting tyrosine phosphorylation, and hence activation of growth factor receptors), as well inducing the selective apoptosis of a number of cancer cell lines, such as colon and lung cancer, (by increasing caspase activity, increasing the uptake of oxidizable substrates into the mitochondria and changing the ratio of the apoptotic-related protein Bax/Bcl-2) (Choi et al, 2009;Dozio et al, 2010;Michikoshi et al, 2013;Na et al, 2009;Wenzel et al, 2005). These properties could help to augment those of the drug and result in a greater inhibition of tumor cell growth.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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Mixed micelles of lipoic acid-chitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery

Elsaid¹,

Taylor²,

Puri

et al. 2017

European Journal of Pharmaceutical Sciences

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Mixed micelles of lipoic acidchitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Phasci(2017Phasci( ), doi: 10.1016Phasci( / j.ejps.2017 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T 2 AbstractMany chemotherapeutics suffer from poor aqueous solubility and tissue selectivity.Distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG) micelles are a promising formulation strategy for the delivery of hydrophobic anticancer drugs. However, storage and in vivo instability restrict their use. The aim of this study was to prepare mixed micelles, containing a novel polymer, lipoic acid-chitosan-poly(ethylene glycol) (LACPEG), and DSPE-PEG, to overcome these limitations and potentially increase cancer cell internalisation. Drug-loaded micelles were prepared with a model tyrosine kinase inhibitor and characterized for size, surface charge, stability, morphology, drug

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Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Accepted Manuscriptmentioning

confidence: 99%

Mixed micelles of lipoic acid-chitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery

Elsaid¹,

Taylor²,

Puri

et al. 2017

European Journal of Pharmaceutical Sciences

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“…Because of these characteristics, α-LA has been used or proposed for the treatment of liver disease, diabetes, and ischemic tissue damage [7][8][9][10]. On the other hand, previous studies have indicated that α-LA suppresses the proliferation of different types of tumor cells such as breast cancer, hepatoma, leukemic, colon, and lung cancer cells, predominantly through facilitating apoptosis [11][12][13][14][15][16][17][18][19]. Different mechanisms have been proposed to account for the increase in apoptotic tumor cell death by α-LA.…”

Section: Introductionmentioning

confidence: 99%

α-Lipoic acid-induced inhibition of proliferation and met phosphorylation in human non-small cell lung cancer cells

et al. 2013

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α-Lipoic acid (α-LA), a naturally occurring anti-oxidant and co-factor for metabolic enzymes, suppresses the growth of different types of tumor cells. The mechanisms that are responsible for these results, however, remain to be elucidated. In the present study, we investigated the effects of α-LA on the proliferation and activation status of definitive receptor tyrosine kinases, epidermal growth factor receptor (EGFR) and Met/hepatocyte growth factor (HGF) receptor, in gefitinib-sensitive human non-small cell lung cancer cells harboring EGFRs with an activating mutation. The enantiomers R-α-LA and S-α-LA suppressed cell proliferation and increased the level of reactive oxygen species in HCC-827 and PC-9 human non-small cell lung cancer cells in an indistinguishable dose-dependent fashion. A phospho-receptor tyrosine kinase array and cell cycle analysis indicated that α-LA decreased tyrosine phosphorylation levels of EGFR, ErbB2, and Met, and this was associated with an inhibition in the cell-cycle transition from the G1 phase to the S phase without inducing apoptosis. Gefitinib, an inhibitor for EGFR tyrosine kinase, inhibited EGFR tyrosine phosphorylation/activation and proliferation of the cells. Instead, the addition of HGF induced Met tyrosine phosphorylation, and this was associated with a resistance to gefitinib-induced growth inhibition, which meant a gain in proliferative ability. In the presence of gefitinib and HGF, the addition of α-LA suppressed Met tyrosine phosphorylation, and this was associated with an inhibition in cell growth. These results suggest that the suppression of tyrosine phosphorylation/activation of growth factor receptors that is critical for the proliferation of human non-small cell lung cancer cells is a mechanism by which α-LA exerts growth inhibition for cancer cells.

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“…α-lipoik asit, doğal antioksidan lipofilik bir bileşiktir (Bilska, 2005). Kanser hücrelerinde, mesane, meme, kolon, hepatoma ve akciğer kanseri hücrelerinin proliferasyonunu, normal hücreleri etkilemeksizin baskılar (Feurecker, 2012, Yoo, 2013, Na, 2009, Michikoshi, 2013, Dozio, 2010, Schwartz, 2013.…”

Section: Discussionunclassified

“…HT-29 kolon kanser hücrelerinde α-lipoik asit ve dihidroksilipoik asitin apoptozu efektif olarak tetiklediği gösterilmiştir (Wenzel, 2005). α-lipoik asit, MCF-7 meme kanseri hücreleri, HepG2 hepatoma (Simbula et al 2007), Jurkat T-lemfoma hücreleri (van de Mark, 2003) gibi pek çok hücre tipinde proapoptotik etkiler sergiler (Dozio, 2010). Bu çalışmada, α-lipoik asit ve L-karnitin'in yalnız ve kombinasyon halinde, HCT 116 +/+ and HCT 116 -/-kolon kanser hücrelerinde sitotoksik etkileri değerlendirilmiştir.…”

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L-Karnitin ve alfa-lipoik asitin, HCT 116 +/+ ve -/- kolon kanser hücre serilerinin proliferasyonu üzerindeki sinerjetik etkileri

KARABAY¹

2016

Ankara Sa

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ÖzetL-karnitin, uzun zincirli yağ asitlerinin mitokondri matriksine transportunda yer alarak, lipid metabolizmasında önemli görevlere sahip olan bir molekül olmasının yanı sıra, serbest radikal temizleyici aktivite gösterir ve antikanser özellikler sergiler. α-Lipoik asitin, tip2 diyabet, ateroskleroz, inflamatuar deri hastalıkları ve Parkinson hastalığına karşı oldukça etkili bir molekül olduğu gösterilmiştir ve farklı kanser hücrelerinde apoptotik etkiler gösterdiği bilinmektedir. Bu çalışmada, α-Lipoik asit ve L-Karnitin'in, HCT 116 +/+ ve HCT 116 -/-kolon kanseri hücre serilerindeki sinerjetik etkileri araştırılmıştır. Bu amaçla, HCT 116 +/+ ve -/-kolon kanseri hücreleri, L-karnitin ve α-Lipoik asit ile 24 saat muamele edildikten sonra, MTT testi ve kaspaz 3-enzim aktivitesi ile hücre canlılığı ve kaspaz-3 enzim aktivitesi üzerindeki etkileri incelenmiştir. Bu çalışmada, α-Lipoik asit ve Lkarnitin'in, kombinasyon halinde verildiklerinde sinerjetik etkiler sergileyerek, HCT 116 +/+ ve -/-kolon kanseri hücrelerinin canlılığını azalttıkları ve kaspaz-3 enzim aktivitesini artırdıkları görülmüştür. L-karnitin ve α-Lipoik asitin kanser terapisindeki sinerjetik etkilerinin mekanizmasını açığa çıkarmak için daha ileri çalışmalar yapılmalıdır.

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The natural antioxidant alpha-lipoic acid induces p27Kip1-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells

Cited by 88 publications

References 36 publications

Mixed micelles of lipoic acid-chitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery

Mixed micelles of lipoic acid-chitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery

α-Lipoic acid-induced inhibition of proliferation and met phosphorylation in human non-small cell lung cancer cells

L-Karnitin ve alfa-lipoik asitin, HCT 116 +/+ ve -/- kolon kanser hücre serilerinin proliferasyonu üzerindeki sinerjetik etkileri

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