Tanshinone IIA inhibits human breast cancer MDA-MB-231 cells by decreasing LC3-II, Erb-B2 and NF-κBp65

Su, Chin‐Cheng; Chien, Su‐Yu; Kuo, Shou‐Jen; Chen, Yao‐Li; Cheng, Chun-Yuan; Chen, Dar‐Ren

doi:10.3892/mmr.2012.756

Cited by 29 publications

(26 citation statements)

References 9 publications

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“…Tan-IIA has anti-cancer [Kapoor, 2009], anti-inflammatory activities [Fan et al, 2009;Ren et al, 2010;Yin et al, 2012], inhibits breast cancer growth in vitro and in vivo [Wang et al, 2005;Su and Lin, 2008;Kapoor, 2009;Gong et al, 2012;Su et al, 2012;Yan et al, 2012]. Its anti-inflammatory activity was associated with inhibition of inflammatory cytokine expressions [Jang et al, 2003;Su and Lin, 2008;Fan et al, 2009;Wang et al, 2010;Tang et al, 2011;Sun et al, 2012;Wu et al, 2012;Xu et al, 2012;Yin et al, 2012].…”

Section: Discussionmentioning

confidence: 99%

“…in vitro and in vivo. Down-regulation or attenuation expressions of IL-6 and NF-kB is a potential therapeutic strategy for cancers Hafeez et al, 2012;Korkaya et al, 2011b], including breast cancer [Leslie et al, 2010;Liu et al, 2010;Jiang et al, 2011;Shostak and Chariot, 2011;Su et al, 2012]. The anti-inflammatory of effect Tan-IIA was associated with inhibition of inflammatory cytokines, such as IL-6 [Jang et al, 2003;Fan et al, 2009;Sun et al, 2012;Yin et al, 2012], and NF-kB [Su and Lin, 2008;Wang et al, 2010;Tang et al, 2011;Sun et al, 2012;Wu et al, 2012;Xu et al, 2012].…”

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confidence: 99%

“…The anti-inflammatory of effect Tan-IIA was associated with inhibition of inflammatory cytokines, such as IL-6 [Jang et al, 2003;Fan et al, 2009;Sun et al, 2012;Yin et al, 2012], and NF-kB [Su and Lin, 2008;Wang et al, 2010;Tang et al, 2011;Sun et al, 2012;Wu et al, 2012;Xu et al, 2012]. Down-regulation or attenuation expressions of IL-6 and NF-kB is a potential therapeutic strategy for cancers Hafeez et al, 2012;Korkaya et al, 2011b], including breast cancer [Leslie et al, 2010;Liu et al, 2010;Jiang et al, 2011;Shostak and Chariot, 2011;Su et al, 2012].…”

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confidence: 99%

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Tanshinone IIA inhibits breast cancer stem cells growth in vitro and in vivo through attenuation of IL‐6/STAT3/NF‐kB signaling pathways

Lin

Wang

et al. 2013

J of Cellular Biochemistry

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Cancer stem cells (CSCs) are maintained by inflammatory cytokines and signaling pathways. Tanshinone IIA (Tan-IIA) possesses anti-cancer and anti-inflammatory activities. The purpose of this study is to confirm the growth inhibition effect of Tan-IIA on human breast CSCs growth in vitro and in vivo and to explore the possible mechanism of its activity. Human breast CSCs were enriched and expanded under serum-free mammosphere culture condition, and identified through mammosphere formation, toluidine blue staining, immunofluorescence staining, and flow cytometry analysis of stemness markers of CD44/CD24 and ALDH, and tumorigenecity in vivo; the growth inhibition effect of Tan-IIA on human breast CSCs in vitro were tested by cell proliferation and mammosphere formation assays; inflammatory signaling pathway related protein expression in response to Tan-IIA, IL-6, STAT3, phospho-STAT3 (Tyr705), NF-κBp65 in cytoplasm and nucleus and cyclin D1 were evaluated with Western blotting; the growth inhibition effect of Tan-IIA on human breast CSCs growth were tested in vivo. A useful model of human breast CSCs for researching and developing the agents targeting CSCs was established. After Tan-IIA treatment, cell proliferation and mammosphere formation of CSCs were decreased significantly; the expression levels of IL-6, STAT3, phospho-STAT3 (Tyr705), NF-κBp65 in nucleus and cyclin D1 proteins were decreased significantly; the tumor growth and mean tumor weight were reduced significantly. Tan-IIA has the potential to target and kill CSCs, and can inhibit human breast CSCs growth both in vitro and in vivo through attenuation of IL-6/STAT3/NF-kB signaling pathways.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Tanshinone IIA inhibits breast cancer stem cells growth in vitro and in vivo through attenuation of IL‐6/STAT3/NF‐kB signaling pathways

Lin

Wang

et al. 2013

J of Cellular Biochemistry

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“…The concentrations triggering eryptosis are within the range of tanshinone IIA plasma concentrations presumably approached in vivo. In mice, a dosages of 3 -100 mg/kg tanshinone IIA have been administrated [12,22,[50][51][52][53][54][55]. Following the application of 8 mg/kg, the plasma concentration increased up to some 3 [M [1].…”

Section: Discussionmentioning

confidence: 99%

Tanshinone IIA Stimulates Erythrocyte Phosphatidylserine Exposure

Zelenak

Pasham

Jilani

et al. 2012

Cell Physiol Biochem

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Tanshinone IIA, an antimicrobial, antioxidant, antianaphylactic, antifibrotic, vasodilating, antiatherosclerotic, organo-protective and antineoplastic component from the rhizome of Salvia miltiorrhiza, is known to trigger apoptosis of tumor cells. Tanshinone IIA is effective in part through mitochondrial depolarization and altered gene expression. Erythrocytes lack mitochondria and nuclei but may undergo eryptosis, an apoptosis-like suicidal cell death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the cell surface. Eryptosis is triggered by increase of cytosolic Ca²⁺ activity, ATP depletion and ceramide formation. The present study explored, whether tanshinone IIA elicits eryptosis. Cytosolic Ca²⁺-concentration was determined from Fluo3-fluorescence, cell volume from forward scatter, phosphatidylserine exposure from binding of fluorescent annexin V, hemolysis from hemoglobin concentration in the supernatant, ATP concentration utilizing luciferin–luciferase and ceramide formation utilizing fluorescent anticeramide antibodies. Clearance of circulating erythrocytes was estimated by CFSE-labeling. A 48 h exposure to tanshinone IIA (≥10 µM) significantly increased cytosolic Ca²⁺-concentration, decreased ATP concentration (25 µM), increased lactate concentration (25 µM), increased ceramide formation (25 µM), decreased forward scatter, increased annexin-V-binding and increased (albeit to a much smaller extent) hemolysis. The effect of 25 µM tanshinone IIA on annexin-V binding was partially reversed in the nominal absence of Ca²⁺. Labelled tanshinone IIA-treated erythrocytes were more rapidly cleared from the circulating blood in comparison to untreated erythrocytes. The present observations reveal a completely novel effect of tanshinone IIA, i.e. triggering of Ca²⁺ entry, ATP depletion and ceramide formation in erythrocytes, events eventually leading to eryptosis with cell shrinkage and cell membrane scrambling.

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“…When effected on an MDA-MB-231 xenograft animal model, tanshinone IIA resulted in a reduction in tumor size and weight with the downregulation of NF-κB p65 and upregulation of caspase-3 compared to the control group. 69 While compared with tanshinone IIA, tanshinone I was more sensitive in inhibiting the growth of MCF-7 and especially MDA-MB-231 cell lines in part by downregulation of Aurora A expression and function. Therefore, Aurora A perhaps was an important functional target of tanshinone I action.…”

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confidence: 99%