Sanguinarine, a Benzophenanthridine Alkaloid, Induces Apoptosis in MDA-MB-231 Human Breast Carcinoma Cells through a Reactive Oxygen Species-Mediated Mitochondrial Pathway

Choi, Woo-Yong; Kim, Gi‐Young; Lee, Won Ho; Choi, Yung Hyun

doi:10.1159/000149719

Cited by 81 publications

(53 citation statements)

References 41 publications

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“…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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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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“…[16,20,23,24,26]. 최근 본 연구실의 결과에 의하면, sanguinarine은 교아종(glioblastoma) 세포에서 mitogen activated 생성 의존적 미토콘드리아 활성화를 통하여 일어났음을 알 수 있었고 [7], 인체 유방암세포의 전이 억제는 치밀 결합(tight junction)의 활성 증가와 matrix metalloproteinase 활성 증가 와 연관성이 있었다 [6]. 아울러 인체 방광암과 대장암세포에서 sanguinarine에 의한 apoptosis 유발은 early growth response gene-1 전사활성 증대를 통한 ROS 생성 의존적이었음을 보고 한 바 있다 [13,14].…”

Section: 서 론unclassified

“…아울러 인체 방광암과 대장암세포에서 sanguinarine에 의한 apoptosis 유발은 early growth response gene-1 전사활성 증대를 통한 ROS 생성 의존적이었음을 보고 한 바 있다 [13,14]. 특히 sanguinarine은 인체 위암세포에서 TRAIL 매개 apoptosis를 촉진할 수 있음 확인한 바 있는데, 이 과정은 PI3K/Akt 경로 억제 및 caspase-3의 활성 증가가 관여하고 있음을 알 수 있었으며 [5,7,12,16,21], 이러한 TRAIL 감수성 증대는 유방암세포에서도 확인된 바 있다 [21]. RNAs were isolated and reverse-transcribed.…”

Section: 서 론unclassified

“…3). Sanguinarine 및 TRAIL 복합처리에 의한 apoptosis 유 발에서 ROS의 역할 다음은 유방암세포를 이용한 선행 연구에서 sanguinarine 에 의한 apoptosis 유발에 ROS의 생성이 필수적으로 동반된 다는 보고 [7,13,14,16,21,24]를 바탕으로, sanguinarine과 TRAIL 복합처리에 의한 AGS 세포의 apoptosis 유발에서도 ROS 생성이 관련되어 있는지의 여부를 조사하였다. [3, 7, 11, 12-14, 16, 20, 21, 24] …”

Section: Sanguinarine과 Trail의 복합처리에 의한 Dr5 발현의 증가unclassified

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Sanguinarine Increases Sensitivity of Human Gastric Adenocarcinoma Cells to TRAIL-mediated Apoptosis by Inducing DR5 Expression and ROS Generation

Lee¹,

Im²,

Choi³

et al. 2014

Journal of Life Science

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Sanguinarine, a benzophenanthridine alkaloid originally derived from the root of Sanguinaria canadensis, has been shown to possess antimicrobial, antioxidant, and anti-cancer properties. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in cancer cells, but not most normal cells and has shown efficacy in a phase 2 clinical trial, development of resistance to TRAIL by tumor cells is a major roadblock. Our previous study indicated that treatment with TRAIL in combination with subtoxic concentrations of sanguinarine sensitized TRAIL-mediated apoptosis in TRAIL-resistant human gastric carcinoma AGS cells; however, the detailed mechanisms are not fully understood. In this study, we show that sanguinarine sensitizes AGS cells to TRAILmediated apoptosis as detected by MTT assay, agarose gel electrophoresis, chromatin condensation and flow cytometry analysis. Combined treatment with sanguinarine and TRAIL effectively induced expression of death receptor (DR) 5 but did not affect expression of DR4 and mitogen activated protein kinases signaling molecules. Moreover, the combined treatment with sanguinarine and TRAIL increased the generation of reactive oxygen species (ROS); however, N-acetylcysteine, ROS scavenger, significantly recovered growth inhibition induced by the combined treatment. Taken together, our results indicate that sanguinarine can potentiate TRAIL-mediated apoptosis through up-regulation of DR5 expression and ROS generation. 다[16, 20, 23, 24, 26]. 최근 본 연구실의 결과에 의하면, sanguinarine은 교아종(glioblastoma) 세포에서 mitogen activated

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“…Its principle medicinal use to date is in dental products based on its anti-bacterial, anti-fungal, and anti-inflammatory activities, which reduce both gingival inflammation and supragingival plaque formation (Godowski, 1989;Kuftinec et al, 1990;Laster and Lobene, 1990). Several recent studies have showed that sanguinarine, at micromolar concentration, inhibits the growth of cancer cells, and this inhibition of growth is associated with cell cycle arrest and the stimulation of apoptosis (Ahsan et al, 2007;Choi et al, 2008;Han et al, 2013a;Jang et al, 2009). The aim of this study is to determine in vitro effect of sanguinarine against neuroblastoma and to question which apoptotic genes contributes its apoptotic effect.…”

Section: Introductionmentioning

confidence: 98%

Promoting Effects of Sanguinarine on Apoptotic Gene Expression in Human Neuroblastoma Cells

Çeçen¹,

Altun²,

Erçetin³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Neuroblastoma is the most common extracranial solid tumor in children. Approximately half of the affected patients are diagnosed with high-risk poor prognosis disease, and novel therapies are needed. Sanguinarine is a benzophenanthridine alkaloid which has anti-microbial, anti-oxidant and anti-inflammatory properties. The aim of this study is whether sanguinarine has in vitro apoptotic effects and which apoptotic genes might be affected in the human neuroblastoma cell lines SH-SY5Y (N-myc negative), Kelly (N-myc positive, ALK positive), and SK-N-BE(2). Cell viability was analysed with WST-1 and apoptotic cell death rates were determined using TUNEL. After RNA isolation and cDNA conversion, expression of 84 custom array genes of apoptosis was determined. Sanguinarine caused cell death in a dose dependent manner in all neuroblastoma cell lines except SK-N-BE(2) with rates of 18% in SH-SY5Y and 21% in Kelly human neuroblastoma cells. Cisplatin caused similar apoptotic cell death rates of 16% in SH-SY5Y and 23% in Kelly cells and sanguinarine-cisplatin combinations caused the same rates (18% and 20%). Sanguinarine treatment did not affect apoptototic gene expression but decreased levels of anti-apoptotic genes NOL3 and BCL2L2 in SH-SY5Y cells. Caspase and TNF related gene expression was affected by the sanguinarine-cisplatin combination in SH-SY5Y cells. The expression of regulation of apoptotic genes were increased with sanguinarine treatment in Kelly cells. From these results, we conclude that sanguinarine is a candidate agent against neuroblastoma.

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Sanguinarine, a Benzophenanthridine Alkaloid, Induces Apoptosis in MDA-MB-231 Human Breast Carcinoma Cells through a Reactive Oxygen Species-Mediated Mitochondrial Pathway

Cited by 81 publications

References 41 publications

Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives

Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives

Sanguinarine Increases Sensitivity of Human Gastric Adenocarcinoma Cells to TRAIL-mediated Apoptosis by Inducing DR5 Expression and ROS Generation

Promoting Effects of Sanguinarine on Apoptotic Gene Expression in Human Neuroblastoma Cells

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