<p>Sanguinarine exhibits potent efficacy against cervical cancer cells through inhibiting the STAT3 pathway in vitro and in vivo</p>

Abstract

Background Cervical cancer is the third most common malignancy among female cancer patients worldwide. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which regulates a variety of cancer cellular physiological activities including cervical cancer. Sanguinarine (SNG) is a natural plant-derived benzophenanthridine alkaloid that possesses antitumor activities in several cancer cells. However, its anticancer effect on human cervical cancer cells and the underlying mechanisms have not been fully defined. Methods In this study, the inhibitory effect of SNG on the proliferation and growth of HeLa cell was detected by MTT assay. Next, cell cycle and apoptosis of HeLa cells was analyzed using Annexin-V/PI double staining and flow cytometry. Then, we measured intracellular ROS generation induced by SNG in HeLa cells by DCFH-DA (10 μM) staining, and the expression level of p-STAT3 and STAT3 was detected by Western blot. Finally, in order to study the effect of SNG on tumor growth in vivo, athymic nude mice were used in the vivo experiments. Result This study showed that SNG dose-dependently decreased the tumor cell proliferation and induced a marked increase in cell apoptosis in HeLa cells. Western blot analysis results revealed that SNG-induced antitumor effect might be mediated by STAT3 inhibition. SNG increased the expression of the proapoptotic protein Bax and reduced the expression of the antiapoptotic protein Bcl-2. We further found that SNG dose-dependently increased ROS level in Hela cells. Moreover, pretreatment with N-acetyl-l-cysteine, a scavenger of ROS, almost reversed the SNG-induced anticancer effect. In addition, SNG inhibited human cervical cancer xenograft growth without exhibiting toxicity in vivo. Conclusion Our findings highlight STAT3 as a promising therapeutic target. We also demonstrate that SNG is a novel anticancer drug for the treatment of cervical cancer.

Sanguinarine Induces Apoptosis in Papillary Thyroid Cancer Cells via Generation of Reactive Oxygen Species

“…STAT3-mediated signaling is often associated with aberrant proliferation and therapeutic resistance of thyroid cancer cells [10,53,54]. Furthermore, STAT3 has been shown to be a major signaling molecule associated with human carcinogenesis, which also causes resistance to cancer therapy and induces stemness [55][56][57][58]; hence, the potential of SNG to suppress the activated STAT3 activity in PTC cells supports its anticancer potential, which is in agreement with previous findings [19,26]. Apoptosis, or programmed cell death, is a vital biological phenomenon essential for homeostasis; it is regulated by a number of signaling proteins, and once deregulated, it leads to the development of various pathological conditions including cancer and therapeutic resistance [59].…”

“…The final step in the synthesis of SNG involves the conversion of precursor dihydrosanguinarine to SNG by the enzyme dihydrobenzophenanthridine oxidase. A number of studies have shown the therapeutic potential of SNG over a range of human pathological and toxicological conditions including cancer; for example, lung cancer [25], cervical cancer [26], gastric cancer [27,28], liver cancer [29,30], multiple myeloma [19], acute lymphoblastic leukemia [31], prostate cancer [32], colorectal cancer [33], ovary cancer [34] and pancreatic cancer [35]. Recently Achkar et al [36] extensively reviewed the anticancer features of SNG and, additionally, antioxidant/anti-inflammatory [37][38][39], antifungal [40,41], antibacterial [42,43], anthelmintic [44] and other pharmacological activities of SNG have also been reported.…”

Crocin treatment promotes the oxidative stress and apoptosis in human thyroid cancer cells FTC‐133 through the inhibition of STAT/JAK signaling pathway

“…This is in agreement with a study in which sanguinarine exhibits potent efficacy against cervical cancer through ROS dependent mitochondrial apoptotic pathway. [ 23 ]…”

The Anticancer Effect of Natural Plant Alkaloid Isoquinolines

“…Chelerythrine-induced apoptosis was accompanied by a decrease in the mitochondrial membrane potential (MMP), the release of cytochrome c, activation of caspase-3 and poly ADP-ribose polymerase (PARP), and downregulation of Bcl-2 in BGC-823 cells [59]. Sanguinarine inhibited tumor growth in vivo and in vitro in various cancers, including prostate [60], cervical [61], pancreatic [62], and colorectal cancers [63]. AsPC-1 and BxPC-3 growth were suppressed via an increase in Bax, Bid, and Bak and decreases in the antiapoptotic Bcl-2 and Bcl-xL proteins [62].…”