Sanguinarine suppresses basal-like breast cancer growth through dihydrofolate reductase inhibition

Kalogris, Cristina; Garulli, Chiara; Pietrella, Lucia; Gambini, Valentina; Pucciarelli, Stefania; Lucci, Cristiano; Tilio, Martina; Zabaleta, María Eléxpuru; Bartolacci, Caterina; Andreani, Cristina; Giangrossi, Mara; Iezzi, Manuela; Belletti, Barbara; Marchini, Cristina; Amici, Augusto

doi:10.1016/j.bcp.2014.05.014

Cited by 57 publications

(31 citation statements)

References 36 publications

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“…SAN is a benzophenanthridine alkaloid found in several plants of the Papaveraceae family, including Chelidonium majus, Bocconia frutescens and Sanguinaria canadensis. Studies have demonstrated that SAN has anticancer effects in various types of cancer, including prostate cancer, osteosarcomas, breast cancer and colorectal cancer (10,13,29,30). In the present study, SAN decreased cell viability in a dose-dependent manner in the human lung adenocarcinoma cell line SPC-A1.…”

Section: Discussionsupporting

confidence: 59%

Sanguinarine-induced apoptosis in lung adenocarcinoma cells is dependent on reactive oxygen species production and endoplasmic reticulum stress

Yang

Xiang

et al. 2015

Oncology Reports

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Sanguinarine (SAN), an alkaloid isolated from plants of the Papaveraceae family, is a compound with multiple biological activities. In the present study, we explored the anticancer properties of SAN in lung cancer using the human lung adenocarcinoma cell line SPC-A1. Our results revealed that SAN inhibited SPC-A1 cell growth and induced apoptosis in a dose-dependent manner. We found that SAN triggered reactive oxygen species (ROS) production, while elimination of ROS by N-acetylcysteine (NAC) reversed the growth inhibition and apoptosis induced by SAN. SAN-induced endoplasmic reticulum (ER) stress resulted in the upregulation of many genes and proteins involved in the unfolded protein response (UPR) pathway, including glucose-regulated protein 78 (GRP78), p-protein kinase R (PKR)-like ER kinase (PERK), p-eukaryotic translation initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4) and CCAAT/enhancer binding protein homologous protein (CHOP). Blocking ER stress with tauroursodeoxycholic acid (TUDCA) markedly reduced SAN-induced inhibition of growth and apoptosis. Furthermore, TUDCA decreased SAN-induced ROS production, and NAC attenuated SAN-induced GRP78 and CHOP expression. Overall, our data indicate that the anticancer effects of SAN in lung cancer cells depend on ROS production and ER stress and that SAN may be a potential agent against lung cancer.

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Section: Discussionsupporting

confidence: 59%

Sanguinarine-induced apoptosis in lung adenocarcinoma cells is dependent on reactive oxygen species production and endoplasmic reticulum stress

Yang

Xiang

et al. 2015

Oncology Reports

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“…Wounding assay was performed as previously described on the same cellular model (A17) 65 . Briefly, a linear wound was produced in A17 confluent cellular population by scratching the bottom of each dish with a sterile pipette tip.…”

Section: Methodsmentioning

confidence: 99%

Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells

Amatori

Mazzoni

Álvarez-Suarez

et al. 2016

Sci Rep

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We describe the biological effects of a polyphenol-rich strawberry extract (PRSE), obtained from the “Alba” variety, on the highly aggressive and invasive basal-like breast cancer cell line A17. Dose-response and time-course experiments showed that PRSE is able to decrease the cellular viability of A17 cells in a time- and dose-dependent manner. PRSE effect on cell survival was investigated in other tumor and normal cell lines of both mouse and human origin, demonstrating that PRSE is more active against breast cancer cells. Cytofluorimetric analysis of A17 cells demonstrated that sub-lethal doses of PRSE reduce the number of cells in S phase, inducing the accumulation of cells in G1 phase of cell cycle. In addition, the migration of A17 cells was studied monitoring the ability of PRSE to inhibit cellular mobility. Gene expression analysis revealed the modulation of 12 genes playing different roles in the cellular migration, adhesion and invasion processes. Finally, in vivo experiments showed the growth inhibition of A17 cells orthotopically transplanted into FVB syngeneic mice fed with PRSE. Overall, we demonstrated that PRSE exerts important biological activities against a highly invasive breast cancer cell line both in vitro and in vivo suggesting the strawberry extracts as preventive/curative food strategy.

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“…Sanguinarine treatment (0.2-2 mol/L for 24 h) blocks cell cycle by enhancing the expression of CDK inhibitors and by reducing not only cyclin D1, D2 and E, but also CDK2, 4 and 6 in human prostate cancer cells [27] . This alkaloid also up-regulates p27 and down-regulates cyclin D1, while inhibiting the activation of STAT3, as demonstrated in vitro in basal cell-like MDA-MB-231 human breast cancer cells and in vivo in a murine breast cancer model [33] . Holy et al [31] studied the effects of sanguinarine (5-10 μmol/L) on the cell cycle regulatory molecules, by immunecytochemistry, that visualized the cyclin D1 and topoisomerase Ⅱ in MCF-7 breast cancer cells.…”

Section: Sanguinarine Induces Alterations In Cell Cyclementioning

confidence: 97%

“…In detail, it has been reported that micromolar concentrations of sanguinarine are capable of inhibiting tumor cell growth, and this inhibitory effect is associated with cell cycle arrest and induction of apoptosis [19][20][21][22] . The anti-proliferative and/ or pro-apoptotic activities of sanguinarine have been demonstrated in in vitro studies on several cancer cell types including epidermal [23] , keratinocyte [24,25] , prostate [26][27][28] , cervical [29] , breast [20,[30][31][32][33] , leukaemia [34,35] , lymphoma [36] , melanoma [37][38][39] , colon [40,41] , colorectal [21] , gastric [42] , pancreatic [19] , lung [22] , neuroendocrine [43] , osteosarcoma [44] , and human neuroblastoma cells [45] . By contrast, there are few studies on the in vivo effectiveness of sanguinarine administration per os [46,47] in animal tumor models [33,48] .…”

Section: Sanguinarine Induces Apoptosis In Tumor Cellsmentioning

confidence: 99%

Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives

Gaziano

Moroni

Buè

et al. 2016

WJGO

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Historically, natural products have represented a significant source of anticancer agents, with plant-derived drugs becoming increasingly explored. In particular, sanguinarine is a benzophenanthridine alkaloid obtained from the root of Sanguinaria canadensis , and from other poppy Fumaria species, with recognized anti-microbial, anti-oxidant and anti-inflammatory properties. Recently, increasing evidence that sanguinarine exibits anticancer potential through its capability of inducing apoptosis and/or antiproliferative effects on tumor cells, has been proved. Moreover, its antitumor seems to be due not only to its pro-apoptotic and inhibitory effects on tumor growth, but also to its antiangiogenic and anti-invasive properties. Although the precise mechanisms underlying the antitumor activity of this compound remain not fully understood, in this review we will focus on the most recent findings about the cellular and molecular pathways affected by sanguinarine, together with the rationale of its potential application in clinic. The complex of data currently available suggest the potential application of sanguinarine as an adjuvant in the therapy of cancer, but further pre-clinical studies are needed before such an antitumor strategy can be effectively translated in the clinical practice.

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Sanguinarine suppresses basal-like breast cancer growth through dihydrofolate reductase inhibition

Cited by 57 publications

References 36 publications

Sanguinarine-induced apoptosis in lung adenocarcinoma cells is dependent on reactive oxygen species production and endoplasmic reticulum stress

Sanguinarine-induced apoptosis in lung adenocarcinoma cells is dependent on reactive oxygen species production and endoplasmic reticulum stress

Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells

Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives

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