Gautam Sethi


Affiliation: National University of Singapore
Country: Singapore


  1. Dai X, Zhang J, Arfuso F, Chinnathambi A, Zayed M, Alharbi S, et al. Targeting TNF-related apoptosis-inducing ligand (TRAIL) receptor by natural products as a potential therapeutic approach for cancer therapy. Exp Biol Med (Maywood). 2015;240:760-73 pubmed publisher
    ..We also briefly discuss combination therapies that have shown great potential in overcoming TRAIL resistance in various tumors. ..
  2. request reprint
    Dai X, Ahn K, Wang L, Kim C, Deivasigamni A, Arfuso F, et al. Ascochlorin Enhances the Sensitivity of Doxorubicin Leading to the Reversal of Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma. Mol Cancer Ther. 2016;15:2966-2976 pubmed
    ..Mol Cancer Ther; 15(12); 2966-76. ©2016 AACR. ..
  3. Merarchi M, Sethi G, Shanmugam M, Fan L, Arfuso F, Ahn K. Role of Natural Products in Modulating Histone Deacetylases in Cancer. Molecules. 2019;24: pubmed publisher
    ..This review will briefly emphasize the potential of natural products in modifying HDAC activity and thereby attenuating initiation, progression and promotion of tumors. ..
  4. Lee J, Kim C, Um J, Sethi G, Ahn K. Casticin-Induced Inhibition of Cell Growth and Survival Are Mediated through the Dual Modulation of Akt/mTOR Signaling Cascade. Cancers (Basel). 2019;11: pubmed publisher
    ..Overall, the findings suggest that CTC can interfere with Akt/mTOR signaling cascade involved in tumorigenesis and can be used together with pharmacological agents targeting Akt/mTOR pathway. ..
  5. Hwang S, Kim C, Lee J, Chinnathambi A, Alharbi S, Shair O, et al. Cycloastragenol can negate constitutive STAT3 activation and promote paclitaxel-induced apoptosis in human gastric cancer cells. Phytomedicine. 2019;59:152907 pubmed publisher
    ..Our results indicate that CAG can function to impede STAT3 activation in human gastric tumor cells and therefore it may be a suitable candidate agent for therapy of gastric cancer. ..
  6. Girisa S, Shabnam B, Monisha J, Fan L, Halim C, Arfuso F, et al. Potential of Zerumbone as an Anti-Cancer Agent. Molecules. 2019;24: pubmed publisher
    ..The current review briefly summarizes the modes of action and therapeutic potential of zerumbone against various cancers. ..
  7. Yang M, Jung S, Sethi G, Ahn K. Pleiotropic Pharmacological Actions of Capsazepine, a Synthetic Analogue of Capsaicin, against Various Cancers and Inflammatory Diseases. Molecules. 2019;24: pubmed publisher
    ..This review briefly summarizes the diverse pharmacological actions of capsazepine against various cancers and inflammatory conditions. ..
  8. Aggarwal V, Kashyap D, Sak K, Tuli H, Jain A, Chaudhary A, et al. Molecular Mechanisms of Action of Tocotrienols in Cancer: Recent Trends and Advancements. Int J Mol Sci. 2019;20: pubmed publisher
    ..e., cellular proliferation, apoptosis, angiogenesis, metastasis, and inflammation have been briefly analyzed. ..
  9. Lee J, Kim C, Lee J, Um J, Sethi G, Ahn K. Arctiin is a pharmacological inhibitor of STAT3 phosphorylation at tyrosine 705 residue and potentiates bortezomib-induced apoptotic and anti-angiogenic effects in human multiple myeloma cells. Phytomedicine. 2019;55:282-292 pubmed publisher

More Information


  1. Jung Y, Shanmugam M, Narula A, Kim C, Lee J, Namjoshi O, et al. Oxymatrine Attenuates Tumor Growth and Deactivates STAT5 Signaling in a Lung Cancer Xenograft Model. Cancers (Basel). 2019;11: pubmed publisher
    ..These results suggest that OMT in combination with paclitaxel can cause an attenuation of lung cancer growth both in vitro and in vivo. ..
  2. Ma Z, Wang Y, Xin H, Wang L, Arfuso F, Dharmarajan A, et al. The expanding roles of long non-coding RNAs in the regulation of cancer stem cells. Int J Biochem Cell Biol. 2019;108:17-20 pubmed publisher
    ..This mini-review also highlights the understanding of the modular regulatory principles of lncRNA interactions in CSCs. ..
  3. Ko J, Arfuso F, Sethi G, Ahn K. Pharmacological Utilization of Bergamottin, Derived from Grapefruits, in Cancer Prevention and Therapy. Int J Mol Sci. 2018;19: pubmed publisher
    ..The present review focuses on the potential anti-neoplastic effects of bergamottin in different tumor models and briefly describes the molecular targets affected by this agent. ..
  4. Bhuvanalakshmi G, Gamit N, Patil M, Arfuso F, Sethi G, Dharmarajan A, et al. Stemness, Pluripotentiality, and Wnt Antagonism: sFRP4, a Wnt antagonist Mediates Pluripotency and Stemness in Glioblastoma. Cancers (Basel). 2018;11: pubmed publisher
    ..This study unveils a novel nuclear role for sFRP4 to promote apoptosis by a possible activation of DNA damage machinery in glioblastoma. ..
  5. Raghunath A, Sundarraj K, Arfuso F, Sethi G, Perumal E. Dysregulation of Nrf2 in Hepatocellular Carcinoma: Role in Cancer Progression and Chemoresistance. Cancers (Basel). 2018;10: pubmed publisher
    ..This review summarizes the role and mechanism(s) of action of Nrf2 dysregulation in HCC and therapeutic options that can be employed to modulate this transcription factor. ..
  6. Jung Y, Hwang S, Sethi G, Fan L, Arfuso F, Ahn K. Potential Anti-Inflammatory and Anti-Cancer Properties of Farnesol. Molecules. 2018;23: pubmed publisher
    ..Furthermore, these findings support the clinical development of farnesol as a potential pharmacological agent in clinical studies. ..
  7. Wee I, Syn N, Sethi G, Goh B, Wang L. Role of tumor-derived exosomes in cancer metastasis. Biochim Biophys Acta Rev Cancer. 2018;1871:12-19 pubmed publisher
    ..We thus intend to end this chapter off by exploring future applications of exosomes that could illuminate shortcomings and propel advancements in biomarker research. ..
  8. Wong A, Xiang X, Ong P, Mitchell E, Syn N, Wee I, et al. A Review on Liquid Chromatography-Tandem Mass Spectrometry Methods for Rapid Quantification of Oncology Drugs. Pharmaceutics. 2018;10: pubmed publisher
    ..In addition, efforts have also been made in this review to address several key aspects in the development of rapid LC-MS/MS methods, including sample preparation, chromatographic separation, and matrix effect evaluation. ..
  9. Lee J, Kim C, Lee S, Sethi G, Ahn K. Ophiopogonin D, a Steroidal Glycoside Abrogates STAT3 Signaling Cascade and Exhibits Anti-Cancer Activity by Causing GSH/GSSG Imbalance in Lung Carcinoma. Cancers (Basel). 2018;10: pubmed publisher
    ..Our findings suggest that OP-D can induce apoptosis and exert anti-tumor effects by inhibition of STAT3 signaling pathways in NSCLC. ..
  10. Merarchi M, Sethi G, Fan L, Mishra S, Arfuso F, Ahn K. Molecular Targets Modulated by Fangchinoline in Tumor Cells and Preclinical Models. Molecules. 2018;23: pubmed publisher
    ..This mini-review briefly describes the potential effects of fangchinoline on important hallmarks of cancer and highlights the molecular targets modulated by this alkaloid in various tumor cell lines and preclinical models. ..
  11. Bordoloi D, Banik K, Shabnam B, Padmavathi G, Monisha J, Arfuso F, et al. TIPE Family of Proteins and Its Implications in Different Chronic Diseases. Int J Mol Sci. 2018;19: pubmed publisher
    ..This review summarizes the vivid role of the TIPE family of proteins and its association with various signaling cascades in diverse chronic diseases. ..
  12. Arora L, Kumar A, Arfuso F, Chng W, Sethi G. The Role of Signal Transducer and Activator of Transcription 3 (STAT3) and Its Targeted Inhibition in Hematological Malignancies. Cancers (Basel). 2018;10: pubmed publisher
    ..e., proliferation, differentiation, migration, and apoptosis of hematological malignancies viz. leukemia, lymphoma and myeloma, and briefly highlights the potential therapeutic approaches developed against STAT3 activation pathway. ..
  13. Wang L, Phan D, Syn N, Xiang X, Song H, Thuya W, et al. A Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Nimbolide in Mouse Serum: Application to a Preclinical Pharmacokinetics Study. Pharmaceutics. 2018;10: pubmed publisher
  14. Shanmugam M, Rane G, Kanchi M, Arfuso F, Chinnathambi A, Zayed M, et al. The multifaceted role of curcumin in cancer prevention and treatment. Molecules. 2015;20:2728-69 pubmed publisher
    ..The current review focuses on the diverse molecular targets modulated by curcumin that contribute to its efficacy against various human cancers. ..
  15. Ko J, Nam D, Um J, Jung S, Sethi G, Ahn K. Bergamottin Suppresses Metastasis of Lung Cancer Cells through Abrogation of Diverse Oncogenic Signaling Cascades and Epithelial-to-Mesenchymal Transition. Molecules. 2018;23: pubmed publisher
    ..BGM treatment also inhibited multiple oncogenic cascades such as PI3K/Akt/mTOR. Overall, the results demonstrate the potential antimetastatic activity of BGM against lung cancer cells. ..
  16. Raghunath A, Sundarraj K, Nagarajan R, Arfuso F, Bian J, Kumar A, et al. Antioxidant response elements: Discovery, classes, regulation and potential applications. Redox Biol. 2018;17:297-314 pubmed publisher
    ..A thorough understanding of AREs will pave the way for the development of therapeutic agents against cancer, neurodegenerative, cardiovascular, metabolic and other diseases with oxidative stress. ..
  17. Kim C, Lee S, Yang W, Arfuso F, Um J, Kumar A, et al. Formononetin-induced oxidative stress abrogates the activation of STAT3/5 signaling axis and suppresses the tumor growth in multiple myeloma preclinical model. Cancer Lett. 2018;431:123-141 pubmed publisher
    ..Overall, our findings indicate that FT exhibits significant anti-cancer effects in MM that may be primarily mediated through the ROS-regulated inhibition of the STAT3 and STAT5 signaling cascade. ..
  18. Puar Y, Shanmugam M, Fan L, Arfuso F, Sethi G, Tergaonkar V. Evidence for the Involvement of the Master Transcription Factor NF-?B in Cancer Initiation and Progression. Biomedicines. 2018;6: pubmed publisher
    ..This review briefly highlights the major mechanisms of NF-?B activation, the role of NF-?B in tumor promotion and suppression, as well as a few important pharmacological strategies that have been developed to modulate NF-?B function. ..
  19. Dai X, Ahn K, Kim C, Siveen K, Ong T, Shanmugam M, et al. Ascochlorin, an isoprenoid antibiotic inhibits growth and invasion of hepatocellular carcinoma by targeting STAT3 signaling cascade through the induction of PIAS3. Mol Oncol. 2015;9:818-33 pubmed publisher
    ..Overall our results indicate that ASC mediates its anti-tumor effects predominantly through the suppression of STAT3 signaling cascade, and can form the basis of novel therapy for HCC patients. ..
  20. Lee J, Kim C, Kim S, Sethi G, Ahn K. Farnesol inhibits tumor growth and enhances the anticancer effects of bortezomib in multiple myeloma xenograft mouse model through the modulation of STAT3 signaling pathway. Cancer Lett. 2015;360:280-93 pubmed publisher
    ..Our results suggest that FOH is a novel blocker of STAT3 signaling pathway and exerts both anti-proliferative and apoptotic activities in MM in vitro and in vivo. ..
  21. Shanmugam M, Dai X, Kumar A, Tan B, Sethi G, Bishayee A. Oleanolic acid and its synthetic derivatives for the prevention and therapy of cancer: preclinical and clinical evidence. Cancer Lett. 2014;346:206-16 pubmed publisher
    ..This review summarizes the diverse molecular targets of OA and its derivatives and also provides clear evidence on their promising potential in preclinical and clinical situations. ..
  22. Monisha J, Roy N, Padmavathi G, Banik K, Bordoloi D, Khwairakpam A, et al. NGAL is Downregulated in Oral Squamous Cell Carcinoma and Leads to Increased Survival, Proliferation, Migration and Chemoresistance. Cancers (Basel). 2018;10: pubmed publisher
    ..Thus, from our study, it is evident that downregulation of NGAL activates the mTOR pathway and helps in the progression of oral cancer. ..
  23. Shanmugam M, Shen H, Tang F, Arfuso F, Rajesh M, Wang L, et al. Potential role of genipin in cancer therapy. Pharmacol Res. 2018;133:195-200 pubmed publisher
    ..These finding suggests that genipin can serve as both a prominent anticancer agent as well as a potent crosslinking drug that may find useful application in several novel pharmaceutical formulations. ..
  24. Sethi G, Shanmugam M, Warrier S, Merarchi M, Arfuso F, Kumar A, et al. Pro-Apoptotic and Anti-Cancer Properties of Diosgenin: A Comprehensive and Critical Review. Nutrients. 2018;10: pubmed publisher
  25. Chai E, Shanmugam M, Arfuso F, Dharmarajan A, Wang C, Kumar A, et al. Targeting transcription factor STAT3 for cancer prevention and therapy. Pharmacol Ther. 2016;162:86-97 pubmed publisher
  26. Bishayee A, Sethi G. Bioactive natural products in cancer prevention and therapy: Progress and promise. Semin Cancer Biol. 2016;40-41:1-3 pubmed publisher
    ..In this special theme issue, contributions from eminent scientists and scholars around the world presented critical analysis of the current progress and promise of natural bioactive constituents in cancer prevention and therapy. ..
  27. request reprint
    Song Z, Shanmugam M, Yu H, Sethi G. Butein and Its Role in Chronic Diseases. Adv Exp Med Biol. 2016;928:419-433 pubmed
    ..Further analysis of its important cellular targets, toxicity, and pharmacokinetic profile may further significantly expand its therapeutic application. ..
  28. Ningegowda R, Shivananju N, Rajendran P, Basappa -, Rangappa K, Chinnathambi A, et al. A novel 4,6-disubstituted-1,2,4-triazolo-1,3,4-thiadiazole derivative inhibits tumor cell invasion and potentiates the apoptotic effect of TNFα by abrogating NF-κB activation cascade. Apoptosis. 2017;22:145-157 pubmed publisher
    ..Overall, these findings indicate a potential novel role and mechanism(s) of action of DTTF as an anticancer agent against diverse malignancies. ..
  29. Ko J, Lee S, Yang W, Um J, Sethi G, Mishra S, et al. The Application of Embelin for Cancer Prevention and Therapy. Molecules. 2018;23: pubmed publisher
    ..Therefore, embelin could be used as a potential agent for cancer therapy. ..
  30. Wang L, Syn N, Subhash V, Any Y, Thuya W, Cheow E, et al. Pan-HDAC inhibition by panobinostat mediates chemosensitization to carboplatin in non-small cell lung cancer via attenuation of EGFR signaling. Cancer Lett. 2018;417:152-160 pubmed publisher
    ..017) alone. These data demonstrate that panobinostat has strong anti-NSCLC activity and chemosensitizes tumors to carboplatin, thus justifying further evaluation of this combination approach in clinical trials. ..
  31. Manu K, Shanmugam M, Ramachandran L, Li F, Siveen K, Chinnathambi A, et al. Isorhamnetin augments the anti-tumor effect of capecitabine through the negative regulation of NF-κB signaling cascade in gastric cancer. Cancer Lett. 2015;363:28-36 pubmed publisher
    ..Overall, our results demonstrate that IH can significantly enhance the anti-tumor effects of capecitabine through the negative regulation of NF-κB regulated oncogenic genes. ..
  32. Roy N, Deka A, Bordoloi D, Mishra S, Kumar A, Sethi G, et al. The potential role of boswellic acids in cancer prevention and treatment. Cancer Lett. 2016;377:74-86 pubmed publisher
    ..Overall, this review projects the pieces of evidence that reveal the potential of boswellic acid as a suitable candidate that can be appropriately developed and designed into a promising anti-cancer drug. ..
  33. Baek S, Ko J, Lee J, Kim C, Lee H, Nam D, et al. Ginkgolic Acid Inhibits Invasion and Migration and TGF-?-Induced EMT of Lung Cancer Cells Through PI3K/Akt/mTOR Inactivation. J Cell Physiol. 2017;232:346-354 pubmed publisher
    ..J. Cell. Physiol. 232: 346-354, 2017. © 2016 Wiley Periodicals, Inc. ..
  34. Zhang J, Rane G, Dai X, Shanmugam M, Arfuso F, Samy R, et al. Ageing and the telomere connection: An intimate relationship with inflammation. Ageing Res Rev. 2016;25:55-69 pubmed publisher
    ..In this review, we aim to summarize the intricate association between the various inflammatory molecules and telomeres that together contribute to the ageing process and related diseases. ..
  35. Thakur K, Saini J, Mahajan K, Singh D, Jayswal D, Mishra S, et al. Therapeutic implications of toll-like receptors in peripheral neuropathic pain. Pharmacol Res. 2017;115:224-232 pubmed publisher
    ..Furthermore, an elaborate discussion on various existing treatment regimens and future targets involving TLRs has also been included. ..
  36. Baek S, Lee J, Kim C, Ko J, Ryu S, Lee S, et al. Ginkgolic Acid C 17:1, Derived from Ginkgo biloba Leaves, Suppresses Constitutive and Inducible STAT3 Activation through Induction of PTEN and SHP-1 Tyrosine Phosphatase. Molecules. 2017;22: pubmed publisher
    ..Overall, GAC 17:1 was found to abrogate STAT3 signaling pathway and thus exert its anticancer effects against multiple myeloma cells. ..
  37. Ko J, Lee J, Jung S, Lee S, Chinnathambi A, Alharbi S, et al. 2,5-Dihydroxyacetophenone Induces Apoptosis of Multiple Myeloma Cells by Regulating the MAPK Activation Pathway. Molecules. 2017;22: pubmed publisher
    ..DHAP also potentiated the pro-apoptotic and anti-proliferative effects of bortezomib in U266 cells. Our results suggest that DHAP can be an effective therapeutic agent to target multiple myeloma. ..
  38. Abbhi V, Saini L, Mishra S, Sethi G, Kumar A, Piplani P. Design and synthesis of benzimidazole-based Rho kinase inhibitors for the treatment of glaucoma. Bioorg Med Chem. 2017;25:6071-6085 pubmed publisher
    ..49?µg/mL in DPPH assay. The molecular docking studies of compound 9j indicated the binding of the compound at the active site of recombinant human ROCK II which makes it a promising antiglaucoma agent. ..
  39. Padmavathi G, Roy N, Bordoloi D, Arfuso F, Mishra S, Sethi G, et al. Butein in health and disease: A comprehensive review. Phytomedicine. 2017;25:118-127 pubmed publisher
    ..Based on numerous preclinical studies, butein shows significant therapeutic potential against various diseases. Nevertheless, well-designed clinical studies are urgently needed to validate the preclinical findings. ..
  40. Shanmugam M, Lee J, Chai E, Kanchi M, Kar S, Arfuso F, et al. Cancer prevention and therapy through the modulation of transcription factors by bioactive natural compounds. Semin Cancer Biol. 2016;40-41:35-47 pubmed publisher
  41. Shanmugam M, Arfuso F, Kumar A, Wang L, Goh B, Ahn K, et al. Modulation of diverse oncogenic transcription factors by thymoquinone, an essential oil compound isolated from the seeds of Nigella sativa Linn. Pharmacol Res. 2018;129:357-364 pubmed publisher
    ..This review focuses on TQ's chemical and pharmacological properties, its diverse molecular targets and also provides clear evidence on its promising potential under preclinical and clinical settings. ..
  42. Mohan C, Bharathkumar H, Bulusu K, Pandey V, Rangappa S, Fuchs J, et al. Development of a novel azaspirane that targets the Janus kinase-signal transducer and activator of transcription (STAT) pathway in hepatocellular carcinoma in vitro and in vivo. J Biol Chem. 2014;289:34296-307 pubmed publisher
    ..Thus, CIMO represents a chemically novel and biologically in vitro and in vivo validated compound, which targets the JAK-STAT pathway as a potential cancer treatment. ..
  43. Siveen K, Sikka S, Surana R, Dai X, Zhang J, Kumar A, et al. Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors. Biochim Biophys Acta. 2014;1845:136-54 pubmed publisher
    ..This review presents the evidence for critical roles of STAT3 in oncogenesis and discusses the potential for development of novel cancer therapies based on mechanistic understanding of STAT3 signaling cascade. ..
  44. Min Wen J, Yan Jiang B, Mishra S, Dai X, Magae J, Shyh Chang N, et al. Molecular Targets of Ascochlorin and Its Derivatives for Cancer Therapy. Adv Protein Chem Struct Biol. 2017;108:199-225 pubmed publisher
  45. Lee H, Baek S, Lee J, Kim C, Ko J, Lee S, et al. Isorhynchophylline, a Potent Plant Alkaloid, Induces Apoptotic and Anti-Metastatic Effects in Human Hepatocellular Carcinoma Cells through the Modulation of Diverse Cell Signaling Cascades. Int J Mol Sci. 2017;18: pubmed publisher
    ..Overall, our results indicate, for the first time, that Rhy could exert anticancer and anti-metastatic effects through regulation of multiple signaling cascades in hepatocellular carcinoma cells. ..
  46. Kanchi M, Shanmugam M, Rane G, Sethi G, Kumar A. Tocotrienols: the unsaturated sidekick shifting new paradigms in vitamin E therapeutics. Drug Discov Today. 2017;22:1765-1781 pubmed publisher
    ..This review provides a comprehensive update on the little-known therapeutic potentials of tocotrienols, which tocopherols lack in a variety of inflammation-driven diseases. ..