Effects of anthocyanins on the AhR–CYP1A1 signaling pathway in human hepatocytes and human cancer cell lines

Kamenickova, Alzbeta; Anzenbacherová, Eva; Pávek, Petr; Soshilov, Anatoly A.; Denison, Michael S.; Zapletalova, Michaela Kopecna; Anzenbacher, Pavel; Dvořák, Zdeněk

doi:10.1016/j.toxlet.2013.05.007

Cited by 31 publications

(26 citation statements)

References 14 publications

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“…This suggests that the mode of action of TCDD on cell proliferation and death differs from that of gemcitabine. TCDD has been demonstrated to activate AHR signaling and thereby regulate the expression of diverse molecules ( 1 - 4 ). The combination of TCDD and gemcitabine may exert a potent antitumor effect, suggesting a novel strategy for cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

2,3,7,8‑Tetrachlorodibenzo‑p‑dioxin suppresses the growth of human liver cancer HepG2 cells in vitro: Involvement of cell signaling factors

Yamaguchi

Hankinson

2018

Int J Oncol

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The aryl hydrocarbon receptor (AHR) is transcriptionally active in the form of a heterodimer with the AHR nuclear translocator, which then binds to the xenobiotic responsive element. AHR was originally discovered via its ligand, the polychlorinated hydrocarbon, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In this study, we investigated whether TCDD regulates the growth of human liver cancer HepG2 cells in vitro. TCDD (0.1–100 nM) was found to exert suppressive effects on the colony formation and proliferation of HepG2 cells, and stimulatory effects on the death of HepG2 cells when the cells reached subconfluence. The effects of TCDD on the HepG2 cells were abolished by culture with CH223191, an inhibitor of AHR signaling. The effects of TCDD were dependent on the concentration of serum, which contains various signaling factors. The effects of TCDD were not potentiated by culture with tumor necrosis factor-α, which activates the signaling of nuclear factor-κB (NF-κB). The results of western blot analysis revealed that TCDD increased the protein levels of p53, Rb, p21, and regucalcin, which are suppressors of the growth of tumor cells. Moreover, TCDD enhanced the NF-κB p65, β-catenin, signal transducer and activator of transcription 3 (STAT3), Ras and Akt levels. Thus, the findings of this study indicate that TCDD may suppress liver cancer cell growth through various signaling pathways, mediated by AHR and its-related co-factors. Of note, the effects of TCDD were found to be potentiated by gemcitabine, which induces nuclear DNA damage in cancer cells, suggesting that their combined use may have potential as a suppressor of tumor cell growth.

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Section: Discussionmentioning

confidence: 99%

2,3,7,8‑Tetrachlorodibenzo‑p‑dioxin suppresses the growth of human liver cancer HepG2 cells in vitro: Involvement of cell signaling factors

Yamaguchi

Hankinson

2018

Int J Oncol

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“…In addition, bilberry-derived C3G was able to inhibit intestinal adenoma formation in an Apc (Min) mouse model (14). Previous preclinical studies have also detected the antitumor efficacy of C3G and P3G (7,(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

Section: Discussionmentioning

confidence: 93%

Anthocyanins inhibit trastuzumab-resistant breast cancer in vitro and in vivo

Tang

et al. 2016

Molecular Medicine Reports

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Trastuzumab (Herceptin®) is a recombinant humanized monoclonal antibody that is targeted against the human epidermal growth factor receptor 2 (HER2) tyrosine kinase receptor. Trastuzumab has been successfully used to treat patients with HER2-positive breast cancer, which accounts for ~25% of invasive breast cancer. However, the majority of patients who initially respond to trastuzumab demonstrate disease progression within 1 year of treatment. Therefore, identifying alternative drugs that overcome trastuzumab resistance and target HER2 may increase the magnitude and duration of response. Through a high‑throughput screening approach, we previously identified numerous anthocyanins that exert activity in HER2‑positive human breast cancer cell lines. The present study aimed to evaluate the anti‑tumor properties of anthocyanins against parental HER2‑positive cells and derivative trastuzumab‑resistant cells in vitro and in vivo. Cell proliferation, western blotting, Annexin V staining, migration and invasion assays were used to determine the effects of anthocyanins in vitro. Cyanidin-3-glucoside and peonidin-3-glucoside were able to inhibit phosphorylation of HER2, induce apoptosis, suppress migration and invasion, and inhibit tumor cell growth. Coupled with the fact that anthocyanins have been used for decades as supplements for the treatment of various types of cancer in Asia, the present study may have established a framework for the development and testing of anthocyanins as a novel treatment paradigm used to overcome classical trastuzumab-resistance and to improve the outcome of this disease.

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“…C3G derived from bilberry also inhibited intestinal adenoma formation in an Apc(Min) mouse model (20). The present study was performed based on the antitumor efficacy potential of C3G and P3G observed in preclinical studies (9)(10)(11)13,14,(16)(17)(18)(19)(20).…”

Section: Discussionmentioning

confidence: 99%

“…P3G and C3G are anthocyanin pigments extracted from black rice (10). P3G and C3G possess anti-cancer properties and have been used as medicine or as supplements for numerous decades (11)(12)(13)(14)(15)(16). P3G and C3G inhibit phospho-HER2 and phospho-AKT and were confirmed to induce HER2-positive breast cancer cell apoptosis in vitro (9).…”

Section: Introductionmentioning

confidence: 99%

Anthocyanins potentiate the activity of trastuzumab in human epidermal growth factor receptor 2-positive breast cancer cells in vitro and in vivo

Liu

et al. 2014

Molecular Medicine Reports

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Human epidermal growth factor receptor 2 (HER2) has been found to be overexpressed in ~25% of invasive breast cancer and is significantly associated with a poor prognosis in breast cancer patients. The anthocyanins cyanidin-3-glucoside (C3G) and peonidin-3-glucoside have been identified as potential drugs for the therapy of HER2‑positive breast cancer. They have been used as supplements in targeted therapeutics and chemotherapeutics in Asia, however, the underlying mechanism remains to be elucidated. The aim of the present study was to investigate the synergism between C3G and trastuzumab (Trast). To address this question, the response to C3G, Trast and a combination of the two drugs, in three representative HER2‑positive cell lines was evaluated. The combination treatments induced apoptosis, inhibited cell growth and affected HER2 and its downstream signaling pathway in MDA‑MB‑453, BT474 and HCC1569 cells, and the effects were synergistic. The combination of 3CG and Trast inhibited tumor growth in an in vivo xenograft model. The data from the present study suggested that C3G exhibits potent antitumor activity when combined with Trast under the investigated conditions.

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Effects of anthocyanins on the AhR–CYP1A1 signaling pathway in human hepatocytes and human cancer cell lines

Cited by 31 publications

References 14 publications

2,3,7,8‑Tetrachlorodibenzo‑p‑dioxin suppresses the growth of human liver cancer HepG2 cells in vitro: Involvement of cell signaling factors

2,3,7,8‑Tetrachlorodibenzo‑p‑dioxin suppresses the growth of human liver cancer HepG2 cells in vitro: Involvement of cell signaling factors

Anthocyanins inhibit trastuzumab-resistant breast cancer in vitro and in vivo

Anthocyanins potentiate the activity of trastuzumab in human epidermal growth factor receptor 2-positive breast cancer cells in vitro and in vivo

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