Effects of daidzein in regards to cytotoxicity in vitro, apoptosis, reactive oxygen species level, cell cycle arrest and the expression of caspase and Bcl-2 family proteins

Han, Bing-Jie; Li, Wei; Jiang, Guang-Bin; Lai, Shang-Hai; Zhang, Cheng; Zeng, Chuan-Chuan; Liu, Yun-Jun

doi:10.3892/or.2015.4133

Cited by 36 publications

(22 citation statements)

References 12 publications

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“…As A549 line has been widely used as a model system to study human alveolar carcinoma, cytotoxic profile of flavonoids in these cells was previously characterized with the results very similar to those measured in our work. Indeed, the IC 50 value of 72.2 µM for quercetin is close to the inhibitory constants published by Loizzo et al (26), Tan et al (27)(28)(29), Robaszkiewicz et al (30), and Chan et al (31); and IC 50 values more than 100 µM were previously reported for fisetin (32), hesperetin (33-35), luteolin (32,36), chrysin (35), baicalein (34), daidzein (37), and genistein (38). Based on our results presented in this article, cytotoxic activity profiles of flavonoids were rather similar for both A549 and HCC-44 lung cancer lines, despite the gender difference of initial origin of these cells.…”

Section: Discussionsupporting

confidence: 86%

Cytotoxic action of methylquercetins in human lung adenocarcinoma cells

et al. 2017

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Abstract. Lung cancer is the malignant disorder associated with a high number of fatalities in women and men worldwide. Despite continuous improvements in diagnostic strategies and therapeutic modalities over the past decades, the prognosis and survival rate of patients suffering from lung cancer are still unsatisfactory and suggest the requirement for further molecular studies with different lung cancer models. In the present study, the anticancer action of two methylated metabolites of quercetin, isorhamnetin and tamarixetin, was assessed by studying their antiproliferative and apoptosis-inducing potential in human lung adenocarcinoma cell lines, A549 and HCC-44. Both methylquercetins decreased the viability of lung cancer cells at doses significantly lower than those effective for parent quercetin. The IC 50 values measured for isorhamnetin were 26.6 and 15.9 µM in A549 and HCC-44 cells, respectively. For tamarixetin, the IC 50 values were 19.6 and 20.3 µM in A549 and HCC-44 cells, respectively. These results were many-fold lower than the respective values for quercetin (72.2 and 107.6 µM for A549 and HCC-44 cells, respectively). Based on the activation of caspase family members, both metabolites induced apoptotic cell death in the tested cell lines, predominantly via the extrinsic pathway in A549 cells and in both intrinsic and extrinsic pathways in HCC-44 cells. As A549 and HCC-44 lines were originally established from a male and female patient, current data may suggst some gender differences in the action of quercetin derivatives. Addition of a methyl group in the 3'-or 4'-position of the B-ring of quercetin significantly increased the anticancer activity of this flavonol towards lung adenocarcinoma cells, which demonstrated that these compounds may be considered as potential novel candidates for the development of future chemotherapeutics in the fight against lung cancer.

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Section: Discussionsupporting

confidence: 86%

Cytotoxic action of methylquercetins in human lung adenocarcinoma cells

et al. 2017

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“…65 For MDA-MB-231, in turn, the effect of the isoflavone is less marked, and does not appear to change significantly for concentrations above 50 µM. 52…”

Section: C3 Ros/rns Measurementmentioning

confidence: 95%

Raman microspectroscopy for probing the impact of a dietary antioxidant on human breast cancer cells

et al. 2016

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Breast cancer is the second most common type of cancer worldwide and the most frequent among women, being the fifth cause of death from neoplastic disease. Since this is an oxidative-stress related neoplasia, it is largely preventable. A dietary isoflavone abundant in soybean -daidzein -was currently investigated as to its chemopreventive and/or chemotherapeutic properties towards the human MDA-MB-231 (metastatic, estrogen-unresponsive) and MCF-7 (estrogen-responsive) breast cancer cell lines. Biological assays for evaluation of antitumour and anti-invasive activities were combined with state-of-theart vibrational microspectroscopy techniques. At 50 and 100 µM concentrations and 48 h incubation time, daidzein was found to induce a marked decrease in cell viability (ca. 50%) for MDA-MB-231 and MCF-7 cells (respectively ca. 50% and 42%) and 40% inhibition of cell migration 48 h. MicroRaman analysis of fixed cells upon exposure to this isoflavone unveiled its metabolic impact on both cell lines. Multivariate data analysis (unsupervised PCA) led to a clear discrimination between control and DAID-exposed cells, with distinctive effects on their biochemical profile, particularly regarding DNA, lipids and protein components, in a cell-dependent way. This is the first reported study on the impact of dietary antioxidants on cancer cells by microRaman techniques. A IntroductionCancer is one of the major causes of morbidity and mortality worldwide, closely following cardiovascular disorders. Breast carcinoma, in particular, is an important public health problem since it is the second most lethal cancer among women worldwide: according to the World Health Organisation (WHO), it affects 28% of the women in Europe 1 , being the second most lethal cancer type in Portugal (16%). 2 Epidemiological evidence has demonstrated a clear difference in breast cancer incidence between eastern and western countries, asian women being the least affected, which can be closely related to dietary habits.Phytochemicals, secondary plant metabolites widespread in fruits, vegetables, cereals and beverages such as tea, coffee and wine, and very abundant in a mediterranean diet, are an abundant source of dietary antioxidants known to significantly decrease the harmful effect of oxidative species, thus being promising chemopreventive agents towards carcinogenesis. [3][4][5][6] Actually, several studies have established a direct relationship between the intake of polyphenols and the prevention of oxidative stress-induced diseases, namely neurodegenerative and cardiovascular disorders, and some types of cancer. 7,8 The isoflavone daidzein (DAID), in particular, is the second most abundant component of soybean (following genistein), a growingly consumed food product, which renders this isoflavone a very suitable target of study regarding its potential health beneficial effects. In addition, it exhibits structural and functional similarities to the endogenous hormone estrogen 9 (Fig. 1). Since some breast cancers are estrogen-dependent (ER + ), DAID may...

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“…It has been reported that Bim plays an important role in cell apoptosis (35)(36)(37). To investigate the potential role of Bim protein in the process of TAM-induced apoptosis, we further determined the Bim expression in TAM-sensitive MCF-7 cells (MCF-7) and TAM-resistant MCF-7 cells (MCF-7R) by Q-PCR and western blot analyses.…”

Section: Bim Is a Pro-apoptosis Effector Of Tam-induced Apoptosis Inmentioning

confidence: 99%

GPER promotes tamoxifen-resistance in ER+ breast cancer cells by reduced Bim proteins through MAPK/Erk-TRIM2 signaling axis

Yin

Zhu

Liu

et al. 2017

International Journal of Oncology

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Tamoxifen resistance is a major clinical challenge in breast cancer treatment. Our previous studies find that GPER and its down-stream signaling play a pivotal role in the development of tamoxifen (TAM) resistance. cDNA array analysis indicated a set of genes associated with cell apoptosis are aberrant in GPER activated and TAM-resistant MCF-7R cells compared with TAM-sensitive MCF-7 cells. Among these genes, Bim (also named BCL2-L11), a member of the BH3-only pro-apoptotic protein family is significantly decreased, and TRIM RING ﬁnger protein TRIM2 (a ubiquitin ligase) is highly expressed in MCF-7R. To understand the mechanism of TAM-resistance in GPER activated ER+ breast cancer, the function of TRIM2 and Bim inducing cell apoptosis was studied. By using immunohistochemical and western blot analysis, there is an adverse correlation between TRIM2 and Bim in TAM-resistant breast tumor tissues and MCF-7R cells. Knockdown Bim in TAM-sensitive MCF-7 cells or overexpression of Bim in TAM-resistant MCF-7 cells significantly changed its sensibility to TAM through altering the levels of cleaved PARP and caspase-3. Activation of GPER and its downstream signaling MAPK/ERK, not PI3K/AKT, led to enhanced TRIM2 protein levels and affected the binding between TRIM2 and Bim which resulted in a reduced Bim in TAM-resistant breast cancer cells. Thus, the present study provides a novel insight to TAM-resistance in ER-positive breast cancer cells.

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Effects of daidzein in regards to cytotoxicity in vitro, apoptosis, reactive oxygen species level, cell cycle arrest and the expression of caspase and Bcl-2 family proteins

Cited by 36 publications

References 12 publications

Cytotoxic action of methylquercetins in human lung adenocarcinoma cells

Cytotoxic action of methylquercetins in human lung adenocarcinoma cells

Raman microspectroscopy for probing the impact of a dietary antioxidant on human breast cancer cells

GPER promotes tamoxifen-resistance in ER+ breast cancer cells by reduced Bim proteins through MAPK/Erk-TRIM2 signaling axis

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