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| 1 | Targeting the PI3K/Akt signaling pathway in gastric carcinoma: A reality for personalized medicine?显示文摘Frequent activation of phosphatidylinositol-3 kinases(PI3K)/Akt/m TOR signaling pathway in gastric cancer(GC) is gaining immense popularity with identification of mutations and/or amplifications of PIK3 CA gene or loss of function of PTEN,a tumor suppressor protein,to name a few; both playing a crucial role in regulating this pathway. These aberrations result in dysregulation of this pathway eventually leading to gastric oncogenesis,hence,there is a need for targeted therapy for more effective anticancer treatment. Several inhibitors are currently in either preclinical or clinical stages for treatment of solid tumors like GC. With so many inhibitors under development,further studies on predictive biomarkers are needed to measure the specificity of any therapeutic intervention. Herein,we review the common dysregulation of PI3K/Akt/m TOR pathway in GC and the various types of single or dual pathway inhibitors under development that might have a superior role in GC treatment. We also summarize the recent developments in identification of predictive biomarkers and propose use of predictive biomarkers to facilitate more personalized cancer therapy with effective PI3K/Akt/m TOR pathway inhibition. | Shikha Satendra Singh Wei Ney Yap Frank Arfuso Shreya Kar Chao Wang Wanpei Cai Arunasalam M Dharmarajan Gautam Sethi Alan Prem Kumar | 2015 | World Journal of Gastroenterology2015，21，43： | 36 |
| 2 | 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 |
| 3 | RNF6 promotes myeloma cell proliferation and survival by inducing glucocorticoid receptor polyubiquitination显示文摘RNF6,a RING-type ubiquitin ligase,has been identified as an oncogene in various cancers but its role in multiple myeloma(MM)remains elusive.In the present study we first showed that the expression levels of RNF6 in MM were significantly elevated compared with the bone marrow cells of healthy donors.Overexpression of RNF6 in LP1 and PRMI-8266 MM cell lines promoted cell proliferation,whereas knockdown of RNF6 led to apoptosis of MM cells.Furthermore,we revealed that RNF6,as a ubiquitin ligase,interacted with glucocorticoid receptor(GR)and induced its K63-linked polyubiquitination.Different from current knowledge,RNF6 increased GR stability at both endogenous and exogenous contexts.Such an action greatly promoted GR transcriptional activity,which was confirmed by luciferase assays and by the increased expression levels of prosurvival genes including Bcl-xL and Mcl-1,two typical downstream genes of the GR pathway.Consistent with these findings,ectopic expression of RNF6 in MM cells conferred resistance to dexamethasone,a typical anti-myeloma agent.In conclusion,we demonstrate that RNF6 promotes MM cell proliferation and survival by inducing atypical polyubiquitination to GR,and RNF6 could be a promising therapeutic target for the treatment of MM. | Ying Ren Xin Xu Chen-yu Mao Kun-kun Han Yu-jia Xu Bi-yin Cao Zu-bin Zhang Gautam Sethi Xiao-wen Tang Xin-liang Mao | 2020 | Acta Pharmacologica Sinica2020，41，3： | 3 |
| 4 | Thymoquinone: Potential cure for inflammatory disorders and cancer显示文摘 | Chern Chiuh Woo Alan Prem Kumar Gautam Sethi Kwong Huat Benny Tan | 2011 | Biochemical Pharmacology2011，，4： | 2 |
| 5 | Suppression of the USP10/CCND1 axis induces glioblastoma cell apoptosis显示文摘Recent studies show that the expression of CCND1,a key factor in cell cycle control,is increased following the progress and deteriotation of glioma and predicts poor outcomes.On the other hand,dysregulated deubiquitinase USP10 also predicts poor prognosis for patients with glioblastoma(GBM).In the present study,we investigated the interplay between CCND1 protein and USP10 in GBM cells.We showed that the expression of CCND1 was significantly higher in both GBM tissues and GBM-derived stem cells.USP10 interacted with CCND1 and prevented its K48-but not K63-linked polyubiquitination in GBM U251 and HS683 cells,which led to increased CCND1 stability.Consistent with the action of USP10 on CCND1,knockdown of USP10 by single-guided RNA downregulated CCND1 and caused GBM cell cycle arrest at the G1 phase and induced GBM cell apoptosis.To implement this finding in the treatment of GBMs,we screened a natural product library and found that acevaltrate(AVT),an active component derived from the herbal plant Valeriana jatamansi Jones was strikingly potent to induce GBM cell apoptosis,which was confirmed by the Annexin V staining and activation of the apoptotic signals.Furthermore,we revealed that AVT concentration-dependently suppressed USP10-mediated deubiquitination on CCND1 therefore inducing CCND1 protein degradation.Collectively,the present study demonstrates that the USP10/CCND1 axis could be a promising therapeutic target for patients with GBMs. | Tong Sun Yu-jia Xu Shuo-yi Jiang Zhuan Xu Bi-yin Cao Gautam Sethi Yuan-ying Zeng Yan Kong Xin-liang Mao | 2021 | Acta Pharmacologica Sinica2021，42，8： | 2 |
| 6 | Butein downregulates chemokine receptor CXCR4 expression and function through suppression of NF-κB activation in breast and pancreatic tumor cells显示文摘 | Angeline Wei Ling Chua Hui Sin Hay Peramaiyan Rajendran Muthu K. Shanmugam Feng Li Pradeep Bist Evelyn S.C. Koay Lina H.K. Lim Alan Prem Kumar Gautam Sethi | 2010 | Biochemical Pharmacology2010，，10： | 1 |
| 7 | 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 |
| 8 | Targeting transcription factor NF- κB to overcome chemoresistance and radioresistance in cancer therapy显示文摘 | Feng Li Gautam Sethi | 2010 | Biochimica et Biophysica Acta (BBA)-reviews on Cancer2010，2，： | 1 |
| 9 | Targeting transcription factor NF-κB to overcome chemoresistance and radioresistance in cancer therapy显示文摘 | Feng Li Gautam Sethi | 2009 | BBA - Reviews on Cancer2009，，2： | 1 |
| 10 | Ursolic acid in cancer prevention and treatment: Molecular targets, pharmacokinetics and clinical studies显示文摘 | Muthu K. Shanmugam Xiaoyun Dai Alan Prem Kumar Benny K.H. Tan Gautam Sethi Anupam Bishayee | 2013 | Biochemical Pharmacology2013，，11： | 1 |
| 11 | β-Caryophyllene oxide inhibits growth and induces apoptosis through the suppression of PI3K/AKT/mTOR/S6K1 pathways and ROS-mediated MAPKs activation显示文摘 | Kyung-Ran Park Dongwoo Nam Hyung-Mun Yun Seok-Geun Lee Hyeung-Jin Jang Gautam Sethi Somi K. Cho Kwang Seok Ahn | 2011 | Cancer Letters2011，，2： | 1 |
| 12 | Celastrol,a novel triterpene,potentiates TNF-induced apoptosis and suppresses invasion of tumor cells by inhibiting NF-κB-regulated gene products and TAKl-mediated NF-κB activation显示文摘 | GAUTAM SETHI KWANG SEOK AHN MANOJ K PANDEY | 2007 | blood2007，，109： | 1 |
| 13 | Targeting transcription factor NF-κB to overcome chemoresistance and radioresistance in cancer therapy显示文摘 | Feng Li Gautam Sethi | 2009 | BBA - Reviews on Cancer2009，，2： | 1 |
| 14 | SJES14110700230368显示文摘 | Sung-Moo Kim Jong Hyun Lee Gautam Sethi Chulwon Kim Seung Ho Baek Dongwoo Nam Won-Seok Chung Sung-Hoon Kim Bum Sang Shim Kwang Seok Ahn | 2014 | Cancer Letters2014，，1： | 1 |
| 15 | Targeting Cell Signaling and Apoptotic Pathways by Dietary Agents: Role in the Prevention and Treatment of Cancer显示文摘 | MuthuK. Shanmugam Radhamani Kannaiyan Gautam Sethi | 2011 | Nutrition and Cancer2011，，2： | 1 |
| 16 | Prospective, Randomized Comparison of Continuous Thoracic Epidural and Thoracic Paravertebral Infusion in Patients With Unilateral Multiple Fractured Ribs—A Pilot Study显示文摘 | Medha Mohta Priyanka Verma Ashok Kr. Saxena Ashok K. Sethi Asha Tyagi Gautam Girotra | 2009 | The Journal of Trauma: Injury Infection and Critical Care2009，，4： | 1 |
| 17 | Butein downregulates chemokine receptor CXCR4 expression and function through suppression of NF-κB activation in breast and pancreatic tumor cells显示文摘 | Angeline Wei Ling Chua Hui Sin Hay Peramaiyan Rajendran Muthu K. Shanmugam Feng Li Pradeep Bist Evelyn S.C. Koay Lina H.K. Lim Alan Prem Kumar Gautam Sethi | 2010 | Biochemical Pharmacology2010，，10： | 1 |
| 18 | Ocotillol Enhanced the Antitumor Activity of Doxorubicin via p53-Dependent Apoptosis显示文摘 | Hongbo Wang Pengfei Yu Jing Bai Jianqiao Zhang Liang Kong Fangxi Zhang Guangying Du Shiqian Pei Lixia Zhang Yongtao Jiang Jingwei Tian Fenghua Fu Gautam Sethi | 2013 | Evidence-Based Complementary and Alternative Medicine2013，，： | 1 |
| 19 | Capillarisin inhibits constitutive and inducible STAT3 activation through induction of SHP-1 and SHP-2 tyrosine phosphatases显示文摘 | Jong Hyun Lee Shu Yuan Chiang Dongwoo Nam Won-Seok Chung Junhee Lee Young-Soon Na Gautam Sethi Kwang Seok Ahn | 2013 | Cancer Letters2013，，： | 1 |
| 20 | Fisetin, a bioactive flavonol, attenuates allergic airway inflammation through negative regulation of NF-κB显示文摘 | Fera Y. Goh Nadine Upton Shouping Guan Chang Cheng Muthu K. Shanmugam Gautam Sethi Bernard P. Leung W.S. Fred Wong | 2012 | European Journal of Pharmacology (-)2012，，1： | 1 |
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