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| 1 | Garcinol sensitizes human head and neck carcinoma to cisplatin in a xenograft mouse model despite downregulation of proliferative biomarkers显示文摘OBJECTIVE Platinum compounds such as cisplatin and carboplatin are frequently used as the first-line chemotherapy for the treatment of the head and neck squamous cell carcinoma(HNSCC).In the present study,we investigated whether garcinol,apolyisoprenylated benzophenone can chemosensitize HNSCC to cisplatin.METHODS The effect of garcinol and cisplatin on HNSCC was assessed by MTT,Western blotting,real time PCR,FACS,immunohistochemistry,DNA binding assay and xenograft mouse model.RESULTS We found that garcinol inhibited the viability of a panel of diverse HNSCC cell lines,enhanced the apoptotic effect of cisplatin,suppressed constitutive as well as cisplatin-induced NF-κB activation,and downregulated the expression of various oncogenic gene products(cyclin D1,Bcl-2,survivin and VEGF).In vivo study showed that administration of garcinol alone(0.5 mg·kg-1,ip five times/week)significantly suppressed the growth of the tumor,and this effect was further increased by cisplatin.Both the markers of proliferation index(Ki-67)and microvessel density(CD31)were downregulated in tumor tissues by the combination of cisplatin and garcinol.The pharmacokinetic results of garcinol indicated that good systemic exposure was achievable after ip administration of garcinol at 0.5and 2mg·kg-1 with mean peak concentration(cmax)of 1825.4 and 6635.7nmol·L-1 in the mouse serum,respectively.CONCLUSION Overall,our results suggest that garcinol can indeed potentiate the effects of cisplatin by negative regulation of various inflammatory and proliferative biomarkers. | Feng Li Muthu K. Shanmugam Kodappully Sivaraman Siveen Fan Wang Tina H. Ong Ser Yue Loo Mahadeva M.M. Swamy Somnath Mandal Alan Prem Kumar Boon Cher Goh Tapas Kundu Kwang Seok Ahn Ling Zhi Wang Kam Man Hui Gautam Sethi | 2015 | 中国药理学与毒理学杂志2015，29，S1： | 4 |
| 2 | Role of macrophages in tumour progression显示文摘 | K.S. Siveen Girija Kuttan | 2009 | Immunology Letters2009，，2： | 2 |
| 3 | Targeting the STAT3 signaling pathway in cancer:role of synthetic and natural inhibitors显示文摘 | Siveen KS Sikka S Surana R | 2014 | Biochim Biophys Acta2014，1845，2： | 1 |
| 4 | Targeting the STAT3 signaling pathway in cancer: Role of synthetic and natural inhibitors显示文摘 | Kodappully Sivaraman Siveen Sakshi Sikka Rohit Surana Xiaoyun Dai Jingwen Zhang Alan Prem Kumar Benny K.H. Tan Gautam Sethi Anupam Bishayee | 2014 | BBA - Reviews on Cancer2014，，2： | 1 |
| 5 | Role of macrophages in tumour progression显示文摘 | Siveen KS Kuttan G | 2009 | Immunol Lett2009，123，2： | 1 |
| 6 | Role of macrophages in tumour progression显示文摘 | Siveen KS Kuttan G | 2009 | Immunol Lett2009，123，2： | 1 |
| 7 | Targeting the stat3 signaling pathway in cancer:Role of synthetic and natural inhibitor,s显示文摘 | Siveen KS Sikka S Surana R | 2014 | Biochim Biophys Acta2014，1845，： | 1 |
| 8 | Augmentation of humoral and cell mediated immune responses by Thujone显示文摘 | Siveen KS Kuttan G | 2011 | Int Immunopharmacol2011，11，12： | 1 |
| 9 | Analysis of the intricate relationship between chronic inflammation and cancer 显示文摘 | Chai E Z Siveen K S Shanmugam M K | 2015 | Biochem2015，468，1： | 1 |
| 10 | Targeting the STAT3 signaling pathway in cancer:role of synthetic and natural inhibitors 显示文摘 | Siveen KS Sikka S Surana R | 2014 | Bio- chimica et Biophysica Acta (BBA) - Reviews on Cancer2014，1845，2： | 1 |
| 11 | Role of macrophages in tumour progression显示文摘 | Siveen KS Kuttan G | 2009 | Immunol Lett2009，123，2： | 1 |
| 12 | Thujone inhibits lung metastasis induced by B16F-10 melanoma cells in C57BL/6 mice显示文摘 | Siveen KS Kuttan G | 2011 | Can J Physiol Phannacol2011，89，10： | 1 |
| 13 | Role of macrophages in tumour progression显示文摘 | Siveen KS Kuttan G | 2009 | Immunol Lett2009，123，2： | 1 |
| 14 | Targeting the STAT3 signaling pathway in cancer:role of synthetic and natural inhibitors 显示文摘 | Siveen KS Sikka S Surana R | 2014 | Biochim Biophys Acta2014，1845，2： | 1 |
| 15 | Negative regulation of signal transducer and activator of transcription- 3 signalling cascade by lupeol inhibits growth and induces apoptosis in hepatocellular carcinoma cells显示文摘 | Siveen KS Nguyen AH Lee JH | 2014 | Br J Cancer2014，111，7： | 1 |
| 16 | Role of macrophages in tmour progression显示文摘 | Siveen KS Kuttan G | 2009 | Immunol Lett2009，123，2： | 1 |
| 17 | Augmentation of humoral and cell mediated immune responses by thujone 显示文摘 | Siveen K S Kuttan G | 2011 | Immunopharm2011，11，12： | 1 |
| 18 | Targe- ting the STAT3 signaling pathway in cancer: Role of synthetic and natural inhibitors 显示文摘 | Kodappully Sivaraman Siveen Sakshi Sikka Surana R etal | 2014 | Biochimica et Biophysica Acta ( BBA ) - Re- views on Cancer2014，1845，2： | 1 |
| 19 | Role of macmphages in tumour progression显示文摘 | Siveen KS Kuttan G | 2009 | Immunol Lett2009，123，2： | 1 |
| 20 | Role of macrophages in tumour progression 显示文摘 | Siveen KS Kuttan G | 2009 | Immunol Lett2009，123，2： | 1 |
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