https://www.ncbi.nlm.nih.gov/pubmed/27671816 Sanguinarine and Its Role in Chronic Diseases. The molecule is endowed with remarkable biological activities and large number of studies on its various activities has been published potentiating its development as a therapeutic agent particularly for chronic human diseases like cancer, asthma, etc. In this article, we review the properties of this natural alkaloid, and its diverse medicinal applications in relation to how it modulates cell death signaling pathways and induce apoptosis through different ways, its utility as a therapeutic agent for chronic diseases and its biological effects in animal and human models.
https://www.ncbi.nlm.nih.gov/pubmed/27363951 Sanguinarine Induces Apoptosis of Human Oral Squamous Cell Carcinoma KB Cells via Inactivation of the PI3K/Akt Signaling Pathway. Preclinical Research Sanguinarine, an alkaloid isolated from the root of Sanguinaria canadensis and other plants of the Papaveraceae family, selectively induces apoptotic cell death in a variety of human cancercells, but its mechanism of action requires further elaboration.
https://www.ncbi.nlm.nih.gov/pubmed/26798435
Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives. 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.
https://www.ncbi.nlm.nih.gov/pubmed/24982522 Owners' perception of the efficacy of Newmarket bloodroot ointment in treating equine sarcoids. In 49 horses with 74 sarcoids, 64 sarcoids responded either completely (n = 49) or partially (n = 15) while 10 did not respond or worsened. Sarcoids < 2 cm responded better to treatment (P < 0.001) than did larger sarcoids.
https://www.ncbi.nlm.nih.gov/pubmed/23499690
Rapid human melanoma cell death induced by sanguinarine through oxidative stress. Pretreatment with glutathione (GSH) also inhibited the anti-melanoma activity of sanguinarine. Thus, pretreatment with the thiol antioxidants NAC and GSH abrogated the killing activity of sanguinarine. Taking together, our data indicate that sanguinarine is a very rapid inducer of human melanoma caspase-dependent cell death that is mediated by oxidative stress.
https://www.ncbi.nlm.nih.gov/pubmed/22215411 Sanguinarine induces apoptosis of HT-29 human colon cancer cells via the regulation of Bax/Bcl-2 ratio and caspase-9-dependent pathway. It was observed that sanguinarine treatment induces a dose-dependent increase in apoptosis of human colon cancer cells.
https://www.ncbi.nlm.nih.gov/pubmed/20032392 Sanguinarine sensitizes human gastric adenocarcinoma AGS cells to TRAIL-mediated apoptosis via down-regulation of AKT and activation of caspase-3. Sanguinarine is a benzophenanthridine alkaloid, derived from the root of Sanguinaria canadensis and other poppy Fumaria species, which is known to have antimicrobial, antiinflammatory and antioxidant properties. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in cancer cells but spare most normal cells.
https://www.ncbi.nlm.nih.gov/pubmed/18560221 Sanguinarine-induced apoptosis in human leukemia U937 cells via Bcl-2 downregulation and caspase-3 activation. Sanguinarine is a benzophenanthridine alkaloid derived from the root of Sanguinariacanadensis, which induces apoptosis in human cancer cells, but the underlying action mechanisms are not completely understood. We investigated the mechanisms of sanguinarine on the induction of apoptosis using U937 leukemia cells.
https://www.ncbi.nlm.nih.gov/pubmed/18189268 Sanguinarine-induced apoptosis: generation of ROS, down-regulation of Bcl-2, c-FLIP, and synergy with TRAIL. Sanguinarine-mediated apoptosis was substantially blocked by ectopic expression of Bcl-2 and cFLIPs. Additionally, we found that sub-lethal doses of sanguinarine remarkably sensitized breast cancercells to TRAIL-mediated apoptosis, but the cell death induced by sanguinarine and TRAIL in combination was not blocked by overexpression of Bcl-2 or Akt. Therefore, combinatory treatment of sanguinarine and TRAIL may overcome the resistance of breast cancer cells due to overexpression of Akt or Bcl-2.
https://www.ncbi.nlm.nih.gov/pubmed/17667597 Induction of apoptosis by sanguinarine in C6 rat glioblastoma cells is associated with the modulation of the Bcl-2 family and activation of caspases through downregulation of extracellular signal-regulated kinase and Akt. The exposure of C6 cells to sanguinarine resulted in growth inhibition and the induction of apoptosis in a dose-dependent manner
https://www.ncbi.nlm.nih.gov/pubmed/17440103 Sanguinarine-dependent induction of apoptosis in primary effusion lymphoma cells. Primary effusion lymphoma (PEL) is an incurable, aggressive B-cell malignancy that develops rapid resistance to conventional chemotherapy. In efforts to identify novel approaches to block proliferation of PEL cells, we found that sanguinarine, a natural compound isolated from the root plant Sanguinariacanadendid, inhibits cell proliferation and induces apoptosis in a dose-dependent manner in several PEL cell lines. Our data show that sanguinarine treatment of PEL cells results in up-regulation of death receptor 5 (DR5) expression via generation of reactive oxygen species (ROS) and causes activation of caspase-8 and truncation of Bid (tBid). Subsequently, tBid translocates to the mitochondria causing conformational changes in Bax, leading to loss of mitochondrial membrane potential and release of cytochrome c to the cytosol. Sanguinarine-induced release of cytochrome c results in activation of caspase-9 and caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage, leading to induction of caspase-dependent apoptosis. In addition, we show that pretreatment of PEL cells with carbobenzoxy-Val-Ala-Asp-fluoromethylketone, a universal inhibitor of caspases, abrogates caspase and PARP activation and prevents cell death induced by sanguinarine. Moreover, treatment of PEL cells with sanguinarine down-regulates expression of inhibitor of apoptosis proteins (IAP). Finally, N-acetylcysteine, an inhibitor of ROS, inhibits sanguinarine-induced generation of ROS, up-regulation of DR5, Bax conformational changes, activation of caspase-3, and down-regulation of IAPs. Taken together, our findings suggest that sanguinarine is a potent inducer of apoptosis of PEL cells via up-regulation of DR5 and raise the possibility that this agent may be of value in the development of novel therapeutic approaches for the treatment of PEL.
https://www.ncbi.nlm.nih.gov/pubmed/17404049 Sanguinarine inhibits VEGF-induced Akt phosphorylation. Sanguinarine (SA), an alkaloid isolated from Sanguinaria canadensis, is known for its antiangiogenetic effects by suppressing basal and VEGF-induced new vessel growth. This article was aimed to evaluate the possible effect of SA (300 nM) on Akt phosphorylation in a porcine aortic endothelial cell line. The alkaloid significantly (P < 0.001) inhibited the VEGF-induced Akt increase, thus suggesting that this mode of action could be responsible, at least partially, for the antiangiogenetic effect of SA.
https://www.ncbi.nlm.nih.gov/pubmed/9312909 [Sanguinarine and ellipticine cytotoxic alkaloids isolated from well-known antitumor plants. Intracellular targets of their action]. Common molecular and cellular targets for alkaloids sanguinarine and ellipticine, isolated from well-known antitumor plants (as well as from their various natural and synthetic derivatives), have been studied and described. Sanguinarine and ellipticine are characterized by significant biological activities including a high antitumor potential.
https://www.ncbi.nlm.nih.gov/pubmed/17196629 Induction of necrosis and apoptosis to KB cancer cells by sanguinarine is associated with reactive oxygen species production and mitochondrial membrane depolarization. These results suggest that sanguinarine has anticarcinogenic properties with induction of ROS production and mitochondrial membrane depolarization, which mediate cancer cell death.
https://www.ncbi.nlm.nih.gov/pubmed/15299076 Sanguinarine causes cell cycle blockade and apoptosis of human prostate carcinoma cells via modulation of cyclin kinase inhibitor-cyclin-cyclin-dependent kinase machinery. These results suggest that sanguinarine may be developed as an agent for the management of prostate cancer.
https://www.ncbi.nlm.nih.gov/pubmed/12912970 Activation of prodeath Bcl-2 family proteins and mitochondrial apoptosis pathway by sanguinarine in immortalized human HaCaT keratinocytes. Taken together, our data showed the involvement of mitochondrial pathway and Bcl-2 family proteins during sanguinarine-mediated apoptosis of immortalized keratinocytes. We suggest that sanguinarine could be developed as a drug for the management of hyperproliferative skin disorders, including skin cancer.
https://www.ncbi.nlm.nih.gov/pubmed/10778985 Differential antiproliferative and apoptotic response of sanguinarine for cancercells versus normal cells. Here we compared the antiproliferative and apoptotic potential of sanguinarine against human epidermoid carcinoma (A431) cells and normal human epidermal keratinocytes (NHEKs). Sanguinarine treatment was found to result in a dose-dependent decrease in the viability of A431 cells as well as NHEKs albeit at different levels because sanguinarine-mediated loss of viability occurred at lower doses and was much more pronounced in the A431 carcinoma cells than in the normal keratinocytes. DNA ladder assay demonstrated that compared to vehicle-treated control, sanguinarine treatment of A431 cells resulted in an induction of apoptosis at 1-, 2-, and 5-microM doses. Sanguinarine treatment did not result in the formation of a DNA ladder in NHEKs, even at the very high dose of 10 microM. The induction of apoptosis by sanguinarine was also evident by confocal microscopy after labeling the cells with annexin V. This method also identified necrotic cells, and sanguinarine treatment also resulted in the necrosis of A431 cells. The NHEKs showed exclusively necrotic staining at high doses (2 and 5 microM).
