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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 | 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 |
| 3 | 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 |
| 4 | Thujone inhibits lung metastasis induced by B16F-10 melanoma cells in C57BL/6 mice显示文摘 | Siveen Kodappully S Kuttan Girija | 2011 | Can J Physiol Pharm2011，89，10： | 1 |
| 5 | The proteome landscape of the root cap reveals a role for the jacalin-associated lectin JAL10 in the salt-induced endoplasmic reticulum stress pathway显示文摘Rapid climate change has led to enhanced soil salinity,one of the major determinants of land degradation,resulting in low agricultural productivity.This has a strong negative impact on food security and environmental sustainability.Plants display various physiological,developmental,and cellular responses to deal with salt stress.Recent studies have highlighted the root cap as the primary stress sensor and revealed its crucial role in halotropism.The root cap covers the primary root meristem and is the first cell type to sense and respond to soil salinity,relaying the signal to neighboring cell types.However,it remains unclear how root-cap cells perceive salt stress and contribute to the salt-stress response.Here,we performed a root-cap cell-specific proteomics study to identify changes in the proteome caused by salt stress.The study revealed a very specific salt-stress response pattern in root-cap cells compared with non-rootcap cells and identified several novel proteins unique to the root cap.Root-cap-specific protein–protein interaction(PPI)networks derived by superimposing proteomics data onto known global PPI networks revealed that the endoplasmic reticulum(ER)stress pathway is specifically activated in root-cap cells upon salt stress.Importantly,we identified root-cap-specific jacalin-associated lectins(JALs)expressed in response to salt stress.A JAL10-GFP fusion protein was shown to be localized to the ER.Analysis of jal10 mutants indicated a role for JAL10 in regulating the ER stress pathway in response to salt.Taken together,our findings highlight the participation of specific root-cap proteins in salt-stress response pathways.Furthermore,root-cap-specific JAL proteins and their role in the salt-mediated ER stress pathway open a new avenue for exploring tolerance mechanisms and devising better strategies to increase plant salinity tolerance and enhance agricultural productivity. | Krishna Kodappully Das Ankita Mohapatra Abin Panackal George Sreenivas Chavali Katja Witzel Eswarayya Ramireddy | 2023 | Plant Communications2023，4，6： | 0 |
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