Sanguinarine Inhibits Vascular Endothelial Growth Factor Release by Generation of Reactive Oxygen Species in MCF-7 Human Mammary Adenocarcinoma Cells

Abstract

The inhibitory action and the possible mechanism of anticancer compound Sanguinarine (SAN) on vascular endothelial growth factor (VEGF) in human mammary adenocarcinoma cells MCF-7 were evaluated in this study. We exposed MCF-7 to SAN for 24 h, then cell viability was assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Human VEGF was measured using a paired antibody quantitative ELISA kit, relative expression of VEGF mRNA was calculated using the real-time PCR studies, and the effect of SAN on the reactive oxygen species (ROS) level was detected by the flow cytometer. Treatment with SAN remarkably inhibited growth of MCF-7 cells and induced cell apoptosis. We found that VEGF release was stimulated by subtoxic concentrations of SAN and inhibited by high dose of SAN, SAN-evoked VEGF release was mimicked by low concentration of H2O2, and SAN-regulated VEGF inhibition was accompanied by increasing of ROS; these changes were abolished by antioxidant. High concentration of SAN inhibited VEGF mRNA expression in MCF-7 cultures, suggesting an effect at transcriptional level, and was also abolished by antioxidant. The present findings indicated that the regulation of VEGF expression and release from MCF-7 cells were possibly through reactive oxygen species evoked by SAN.

Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives

“…Consistently, pre-treatment of tumor cells with antioxidants such as N-acetylcysteine or glutathione counteracts the apoptosis induced by sanguinarine [21,32,37,52] . Moreover, the over-expression of cyclooxygenase-2 (COX-2) also rescues prostate cancer cells from sanguinarine-induced apoptosis by sanguinarine enhances apoptosis in human mammary adenocarcinoma MCF-7 through the inhibition of VEGF release, induced by generation of ROS [32] . Sanguinarine also inhibits angiogenesis in preclinical experimental tumor models, such as mouse melanoma [48] and rat colorectal cancer, as we reported previously [49] .…”

“…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] .…”

TGFβ-Responsive HMOX1 Expression Is Associated with Stemness and Invasion in Glioblastoma Multiforme

“…One testable hypothesis is that since HMOX1 generates carbon monoxide (CO) through enzymatic reaction, it can alter the metabolic state of GBM cells and offset cellular respiration under hypoxic conditions, which would promote the survival and maintenance of CSCs in a nondifferentiated state. In general CO has a cytoprotective effect since it limits excessive production of toxic reactive oxygen species (ROS) in mitochondria by inducing a mild‐uncoupling state .The cytoprotective effect of HMOX1 through CO generation could be adopted by CSCs to reduce ROS levels and survive in the hypoxic region of the tumor. If so, understanding the mechanism for ROS regulation in CSCs may help in the development of powerful therapeutic strategies in future.…”

Natural Products Discovered in a High-Throughput Screen Identified as Inhibitors of RGS17 and as Cytostatic and Cytotoxic Agents for Lung and Prostate Cancer Cell Lines

“…Given that these compounds were identified as inhibitors of RGS17 and that these compounds have reported activities in lung, prostate, hepatocellular carcinoma, and breast cancer, the pathologies in which RGS17 has been reported to play a role, it is possible that inhibition of RGS17 may be one of the many mechanisms by which these compounds alter cancer cell growth. 56–58 Extensive pathway analysis is required to determine exactly what signaling events are being altered in the lung and prostate cell lines used here to determine the primary mechanism of action of these compounds.…”