Bax, Bcl-2, and NF-κB Expression in Sanguinarine Induced Bimodal Cell Death

Weerasinghe, Priya; Hallock, Sarathi; Liepins, Andrejs

doi:10.1006/exmp.2001.2355

Cited by 49 publications

(29 citation statements)

References 32 publications

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“…Studies by others and from our laboratory have shown that sanguinarine modulates Bcl-2 family proteins in favor of apoptosis (21,24,25). Immunoblot analysis showed a significant increase in proapoptotic proteins Bax, Bid, and Bak with a concurrent significant decrease in antiapoptotic proteins Bcl-2 and Bcl-X L when the cells were treated with UVB ( Fig.…”

Section: Sanguinarine Enhances Uvb-mediated Induction Of Apoptosis VImentioning

confidence: 71%

Enhancement of UVB radiation–mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes

Reagan-Shaw¹,

Breur²,

Ahmad

2006

Molecular Cancer Therapeutics

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In this article, we studied the chemopreventive effects of sanguinarine on UVB-mediated responses in human HaCaT immortalized keratinocytes. For our studies, HaCaT cells were treated with a low dose (50 nmol/L) of sanguinarine for 24 hours followed by irradiation with UVB (15 or 30 mJ/ cm 2 ). Our data showed that UVB exposure, at both doses, resulted in decreased cell viability and increased apoptosis. Interestingly, pretreatment of the cells with sanguinarine caused a significant enhancement in the antiproliferative response of UVB. These responses on UVB and/or sanguinarine treatments were associated with (a) decrease in Bcl-2 and Bcl-X L and (b) increase in Bax, Bid, and Bak protein levels. Bax knockdown and Bcl-2 overexpression resulted in a rescue of HaCaT cells from sanguinarine-mediated apoptosis. DNA cell cycle analysis revealed that UVB treatment resulted in an accumulation of cells in the G 2 -M phase of the cell cycle, whereas pretreatment of sanguinarine resulted in a significant shift of cells in the S phase at a low UVB dose and a further accumulation of cells in the G 2 -M phase at a higher UVB dose. These effects on cell cycle were accompanied with modulations in the protein levels of cyclin (B1, E, and A) and cdc2 and cyclindependent kinase 1. Furthermore, sanguinarine treatment was found to result in significant modulations in p53, p66Shc, MsrA, and superoxide dismutase levels. Based on our data, we suggest the sanguinarine may protect skin cells from UVB-mediated damages via apoptotic elimination of damaged cells that escape programmed cell death and therefore possess a potential of clonal expansion.

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Section: Sanguinarine Enhances Uvb-mediated Induction Of Apoptosis VImentioning

confidence: 71%

Enhancement of UVB radiation–mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes

Reagan-Shaw¹,

Breur²,

Ahmad

2006

Molecular Cancer Therapeutics

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“…Sanguinarine-induced apoptosis has been detected in human epidermoid carcinoma (A431) [8] , human prostate cancer (LNCaP, DU-145, PC-3) [22,23] , and breast cancer (MCF-7) cell lines [7] , human endocervical (HeLa) [24] , human melanoma (M4Beu), human colon adenocarcinoma (DLD-1), lung non-small cell carcinoma (A549) [7] , human uveal melanoma (OCM-1) [25] , histiocytic lymphoma (U937), myeloid leukemia (ML-1a) [6] , human erythroleukemia (K562, JM1) cell lines [6,[26][27][28] , immortalized human keratinocytes (HaCaT) [26] and human primary fibroblasts [7,26] . In addition to this information, we found that sanguinarine did not cause ototoxic effect on cochlear cells, while cisplatin caused 20% necrosis on cochlear cells.…”

Section: Discussionmentioning

confidence: 99%

Apoptotic Effects of Sanguinarine on the Organ of Corti 1 Cells: Comparison with Cisplatin

Çeçen¹,

Erçetin²,

Kırkım³

et al. 2015

Int Adv Otol

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OBJECTIVE:Sanguinarine is an alkaloid obtained from the root of Sanguinaria canadensis and other plants from the Papaveraceae family and is well known to possess a broad range of biological functions, such as antimicrobial, antifungal, anti-inflammatory, and antineoplastic activities. We aimed to specify the in vitro effect of sanguinarine on the House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and to compare this effect with the ototoxic effect of cisplatin (CDDP). MATERIALS and METHODS:We performed cell proliferation assay for determining the in vitro effect of sanguinarine alone and compared it with the effect of cisplatin. Flow cytometry annexin-V apoptosis detection was performed. RESULTS:We found that sanguinarine and CDDP inhibited the cell growth in a dose-dependant manner in HEI-OC1 cells after 24 h of incubation. In sanguinarine-treated group, apoptosis was 6.6%, necrosis was 26.7%, and the cell viability was 66.7%. Further, in CDDP-treated group, apoptosis was 5.6%, necrosis was 45.4%, and the cell viability was 48.7%. According to the annexin-V apoptosis detection results, we found that sanguinarine caused 3.9% apoptosis and 1.3% necrosis, while CDDP caused 2.9% apoptosis and 20% necrosis on HEI-OC1 cells. CONCLUSION:Our findings suggested that lower doses of sanguinarine are promising antineoplastic agents, which did not indicate any toxic effect on HEI-OC1 cells. Application of these data to clinical practice requires further support by in vivo studies.

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“…Sanguinarine and chelerythrine contain reactive imine groups and are capable of inhibiting the activity of enzymes and other proteins which possess the nucleophilic groups [8]. Some alkaloids of greater celandine act as protein kinase inhibitors, and block the activity of transcription factor NF-κB involved in signal transduction pathways leading to either cell proliferation or cell death [4,27,28].…”

Section: Introductionmentioning

confidence: 99%

Correlation of the cytotoxic activity of four different alkaloids, from Chelidonium majus (greater celandine), with their DNA intercalating properties and ability to induce breaks in the DNA of NK/Ly murine lymphoma cells

Kaminskyy¹,

Lootsik

Stoika³

2006

Open Life Sciences

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Abstract:The purpose of this study was to examine the relationship between the DNA intercalating characteristics and the DNA damaging capacity of four alkaloids extracted from Chelidonium majus L, as well as their toxicity towards murine NK/Ly lymphoma cells. Chelerythrine, sanguinarine and coptisine were found to be intercalated into the DNA isolated from NK/Ly cells, meanwhile, chelidonine exhibited no affinity to DNA. Sanguinarine exhibited the greatest toxicity toward NK/Ly cells, and the toxicity of the other three decreased in descending order: chelerythrine, coptisine and chelidonine. Chelerythrine and sanguinarine caused DNA damage, illustrated by the formation of comets of the third class. Coptisine was less toxic than chelerythrine and sanguinarine, and affected the formation the same class of comets in higher concentration. The quantity of comets induced by chelidonine were negligible, a finding consistent with its inability to intercalate into DNA structure. The ability of four main alkaloids of Chelidonium majus L., to intercalate into DNA isolated from murine NK/Ly lymphoma cells, correlated with their ability to induce breaks in cellular DNA and with their toxic effect towards those cells.

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Bax, Bcl-2, and NF-κB Expression in Sanguinarine Induced Bimodal Cell Death

Cited by 49 publications

References 32 publications

Enhancement of UVB radiation–mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes

Enhancement of UVB radiation–mediated apoptosis by sanguinarine in HaCaT human immortalized keratinocytes

Apoptotic Effects of Sanguinarine on the Organ of Corti 1 Cells: Comparison with Cisplatin

Correlation of the cytotoxic activity of four different alkaloids, from Chelidonium majus (greater celandine), with their DNA intercalating properties and ability to induce breaks in the DNA of NK/Ly murine lymphoma cells

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