Nitidine Chloride inhibits breast cancer cells migration and invasion by suppressing c-Src/FAK associated signaling pathway

Pan, Xinhua; Han, Hongyu; Wang, Lei; Yang, Li-Ye; Li, Ruimei; Li, Zhenxi; Liu, Junchen; Zhao, Qufei; Qian, Min; Liu, Mingyao; Du, Bing

doi:10.1016/j.canlet.2011.09.001

Cited by 82 publications

(73 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1A) is a pentacyclic alkaloid isolated from Z. nitidium and has been identified as a potential anti-tumor drug because of its topoisomerase I/II inhibit activities (Wang et al, 1993;Holden et al, 1999;Chen et al, 2012). Meanwhile, NTD has also shown anti-metastasis activity through restrain to c-Src/FAK associated signaling pathway in breast cancer cells (Pan et al, 2011). However, the function and mechanism of anti-inflammatory compound in 'liangmianzhen' is not well clarified.…”

Section: Introductionmentioning

confidence: 98%

Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF-kappaB pathway in RAW 264.7 cells

Wang

Jiang

Zhang

et al. 2012

Journal of Ethnopharmacology

Self Cite

107

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 98%

Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF-kappaB pathway in RAW 264.7 cells

Wang

Jiang

Zhang

et al. 2012

Journal of Ethnopharmacology

Self Cite

107

View full text Add to dashboard Cite

“…As a well-known traditional Chinese folk medicine, it is used to promote the flow of Qi, relieve pain, promote blood circulation and to remove blood stasis (27). Nitidine is found in the root of Zanthoxylum nitidum and several studies have demonstrated that nitidine exerts antitumor, anti-inflammatory, anti-leukemic and even anti-HIV effects (28,29). Previous studies on nitidine chloride (NC) have focused on topoisomerase I poison-mediated cell toxicity (30,31).…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies on nitidine chloride (NC) have focused on topoisomerase I poison-mediated cell toxicity (30,31). NC has also been reported to be involved in the suppression of cell growth, the induction of cell apoptosis, cell cycle arrest and the inhibition of the activity of DNA ligases; it exerts its anti-metastatic activity by restraining the c-Src/focal adhesion kinase (FAK)-associated signaling pathway in breast cancer cells (28,31) and NC has been shown to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 production through the suppression of phosphorylation of mitogen-activated protein kinases (MAPKs) and the translocation of p65 (29).…”

Section: Introductionmentioning

confidence: 99%

Nitidine chloride inhibits hepatocellular carcinoma cell growth in vivo through the suppression of the JAK1/STAT3 signaling pathway

Liao

Zheng

et al. 2013

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Abstract. Signal transducer and activator of transcription 3 (STAT3) is persistently activated in cancer cells and contributes to malignant progression in various types of cancer. The Janus-activated kinase (JAK) family phosphorylates STAT3 in response to stimulation by cytokines or growth factors. The JAK1-STAT3 signaling pathway plays an important role in cell proliferation and apoptosis. Nitidine chloride (NC) is a benzophenanthridine alkaloid that has been reported as an antitumor agent due to its its inhibitory effects on topoisomerase I. Using a mouse xenograft model of hepatocellular carcinoma (HCC), this study aimed to evaluate the effects of NC on tumor growth in vivo and to elucidate the underlying mechanisms. The analysis of the effects of NC on apoptosis in HCC tumor xenografts in mice was carried out by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay; the expression of Bcl-2, Bax, cyclin-dependent kinase (CDK)4, cyclin D1, p21 and proliferating cell nuclear antigen (PCNA) was analyzed by immunohistochemistry; and the protein expression of JAK1 and STAT3 was examined by western blot analysis. Our results revealed that treatment with NC decreased the tumor volume and tumor weight, suggesting that NC inhibits HCC cell growth in vivo. In addition, NC blocked the activation of JAK1-STAT3 in the tumor tissues, which in turn resulted in the induction of cancer cell apoptosis and the inhibition of proliferation. Consequently, treatment with NC downregulated the expression of cyclin D1, CDK4 and Bcl-2 and increased the level of p21 and Bax. Our data provide a molecular basis for the antitumor activity of NC. IntroductionHepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide (1,2) and it has been reported that more than 600,000 individuals succumb to the disease each year (1). It is the second most common cause of cancer-related mortality in China, and 75% of known new cases and deaths in the Asia-Pacific region (3-5). Currently, the main treatment methods for liver cancer include surgical resection, radiotherapy and chemotherapy (4,6). Although surgical resection (which involves removing the tumor completely) offers the best prognosis for long-term survival, only 10-15% of patients are suitable for surgical resection, as the tumor may be too large, or may have grown into major blood vessels or other vital organs (7-9). Related data demonstrate that the percentage of HCC cells is already high at diagnosis with a high expression of the multidrug resistance gene and conventional chemotherapy of HCC fails to provide satisfactory remission and may cause serious side-effects (6,10). Thus, it is necessary to develop a novel effective drug for the treatment of HCC. Natural products have attracted much attention in the search for novel anticancer therapeutic agents as they have relatively few side-effects and have long been used as alternative therapies for various diseases, including cancer (11,12). Therefore, determining naturally occurrin...

show abstract

“…The anticancer activity of NC was correlated with its ability to decrease cell growth, induce cell apoptosis, and arrest cell cycles in a variety of human cancer cell lines, such as MG-63 and KB osteosarcoma cell lines (Liu et al, 2007;Xu et al, 2011). Meanwhile, the tumor-selective cytotoxicity of NC was found to be attributed to intercalation into DNA and inhibition of topoisomerase I and II (Gatto et al, 1996;Holden et al, 1999;Iwasaki et al, 2010;Pan et al, 2011). Additionally, NC could inhibit hepatocellular carcinoma cell growth in vivo (Liu et al, 2009;Liao et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

The Contribution of Human OCT1, OCT3, and CYP3A4 to Nitidine Chloride–Induced Hepatocellular Toxicity

Yang

et al. 2014

Drug Metab Dispos

View full text Add to dashboard Cite

Nitidine chloride (NC), a quaternary ammonium alkaloid, has numerous pharmacological effects, such as anticancer activity. However, it was found that NC also has hepatocellular toxicity. Because organic cation transporters 1 and 3 (OCT1 and OCT3) might mediate the influx of NC into hepatocytes, multidrug and toxin extrusion 1 (MATE1) probably mediates the efflux of NC from hepatocytes, while cytochrome P450 (P450) enzymes might contribute to NC metabolism, the present study was to evaluate the contribution of OCT1, OCT3, MATE1, and P450 enzymes to NCinduced hepatocellular toxicity. Our results showed that the uptake of NC in Madin-Darby canine kidney (MDCK) cells expressing human (h) OCT1 and OCT3 (MDCK-hOCT1 and MDCK-hOCT3) was significantly higher than that in mock cells; the hOCT1-and hOCT3-mediated uptake followed typical Michaelis-Menten kinetics.Meanwhile, NC was also a substrate of hMATE1, although its transport capacity was much lower than that of OCT1 NC-induced cytotoxicity in MDCK-hOCT1 or MDCK-hOCT3 cells was obviously higher than that in mock cells. Quinidine and (+)-tetrahydropalmatine [(+)-THP], OCT1 and OCT3 inhibitors, significantly reduced the uptake of NC in MDCK-hOCT1 cells, MDCK-hOCT3 cells, and rat primary hepatocytes, but only (+)-THP markedly attenuated the NCinduced toxicity. In addition, P450 enzymes, such as CYP3A4, mediated the metabolism of NC, and NC-induced toxicity in MDCKhOCT1/hCYP3A4 cells was lower than that in MDCK-hOCT1 cells. Our results indicated that NC is a substrate of hOCT1, hOCT3, and CYP3A4; that OCT1 and OCT3 mediate the uptake of NC in hepatocytes and subsequently cause hepatotoxicity; and that NC-induced toxicity could be attenuated by CYP3A4-mediated metabolism.

show abstract

Nitidine Chloride inhibits breast cancer cells migration and invasion by suppressing c-Src/FAK associated signaling pathway

Cited by 82 publications

References 33 publications

Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF-kappaB pathway in RAW 264.7 cells

Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF-kappaB pathway in RAW 264.7 cells

Nitidine chloride inhibits hepatocellular carcinoma cell growth in vivo through the suppression of the JAK1/STAT3 signaling pathway

The Contribution of Human OCT1, OCT3, and CYP3A4 to Nitidine Chloride–Induced Hepatocellular Toxicity

Contact Info

Product

Resources

About