Position：Vice Chair of Cancer Institute
Medical School：Chinese Academy of Preventive Medicine, China
Post-doctoral training, Center for Biotechnology, Wurzburg University, Wurzburg, Germany
Post-doctoral training, Department of Physiology, Mount Sinai Medical School, New York, USA
Dr. Hu is interested in cancer metabolism by focusing on glucose metabolism and its implication in cancer treatment. Dr. Hu found that lactic acidosis, which is the outcome of cancer glucose metabolism, played very important roles in regulating glucose metabolism. Specifically, with lactic acidosis, cancer cells convert its metabolic phenotype from wasteful Warburg effect to a very efficient metabolic mode, characterized by low rate of glycolysis and negligible generation of lactate. Mechanistically, proton slows down the glycolysis rate while high lactate concentration brings the LDH-catalyzed reaction to a (very near) thermodynamic equilibrium state, thereby blocking a net flux of glucose carbon to lactate. In addition, lactic acidosis conferred cancer cells with resistance to glucose deprivation. Therefore, neutralizing intratumoral lactic acidosis could induce cell death under glucose deprivation and this has potential in cancer therapy. Dr Hu applies this principle to treat hepatocellular carcinoma (HCC). He demonstrated that infusing bicarbonate into HCC via tumor feeding artery dramatically enhanced the efficacy of TACE, and we termed this procedure TILA-TACE (Targeting-Intratumoral-Lactic-Acidosis –TACE). Currently, Dr Hu's team is validating the efficacy of TILA-TACE. In addition, he is investigating the regulation of glucose metabolism by integrating kinetics and thermodynamics.
CM J, XB Zhu, QR Pan, Xun HU* Perturbation of PGK1 only marginally affects glycolysis in cancer cells. J Biol Chem 2020 295(19):6425-6446.
M Y, C GUO, Xun HU*. Quantitative relationship between isotopic and net contribution of lactate and glucose to tricarboxylic acid cycle. J Biol Chem. 2019 294(24):9615-9630.
W Zhang, C Guo, K Jiang, M Ying, Xun Hu* Quantification of lactate from various metabolic pathways and quantification issues of lactate isotopologues and isotopmers. Scientific Reports 2017. DOI:10.1038/s41598-017-08277-3 .
M Chao, H Wu, K Jin, B Li, J Wu, G Zhang, G Yang, Xun Hu* A nonrandomized cohort and a randomized study of local control of large hepatocarcinoma by targeting intratumoral lactic acidosis. eLife DOI: 10.7554/eLife.15691.
J Xie, C Yan, Xun HU* Evidence That Does Not Support Pyruvate Kinase M2 (PKM2)-catalyzed Reaction as a Rate-limiting Step in Cancer Cell Glycolysis. J Biol Chem 2016 291. 8987–8999.
H Wu, M Ying, Xun HU* Lactic acidosis switches cancer cells from aerobic glycolysis back to dominant oxidative phosphorylation Oncotarget DOI: 10.18632/oncotarget.9746.
J Xie, H Wu, C Dai, Q Pan, Z Ding, D Hu, B Ji, Y Luo*, X Hu*. Beyond Warburg effect – dual metabolic nature of cancer cells. Scientific Reports | 4 : 4927 | DOI: 10.1038/srep049271, 2014.
C Zhu, W Hu, H Wu, X Hu*. No evident response relationship between cellular ROS level and its cytotoxicity – a paradoxical issue in ROS-based cancer therapy. Scientific Reports | 4 : 5029 | DOI: 9.1038/srep05029, 2014.
Biao Zhang, Zhen Liu, Xun Hu* Inhibiting cancer metastasis via targeting NAPDH oxidase 4. Biochem Pharmacol 86:253-266, 2014.
Hao Wu, Jiansheng Xie, Qiangrong Pan, Beibei Wang, Danqing Hu, Xun Hu* Anticancer Agent Shikonin Is an Incompetent Inducer of Cancer Drug Resistance. PLoS ONE Volume 8 | Issue 1 | e52706, 2013.
Chunyan Dai, Feifei Sun, Chunpeng Zhu, Xun Hu* Tumor Environmental Factors Glucose Deprivation and Lactic Acidosis Induce Mitotic Chromosomal Instability –An Implication in Aneuploid Human Tumors. PLoS ONE Volume 8 | Issue 5 | e63054, 2013.
Zhen Liu, Biao Zhang, Kun Liu, Zonghui Ding, Xun Hu1* Schisandrin B Attenuates Cancer Invasion and Metastasis Via Inhibiting epithelial-Mesenchymal Transition PLoS ONE Volume 7 | Issue 7 | e40480, 2013.
Hao Wu,Zonghui Ding,† Danqing Hu, Feifei Sun, Chunyan Dai, Jiansheng Xie and Xun Hu* Central role of lactic acidosis in cancer cell resistance to glucose deprivation-induced cell death. J Pathol 227:189-299, 2012.
Jing Chen, Zheng Jiang, Beibei Wang, Yanguang Wang C, Xun Hu* Vitamin K3 and K5 are inhibitors of tumor pyruvate kinase M2. Cancer Lett 316 :204–210, 2012.
Feifei Sun., Chunyan Dai., Jiansheng Xie, Xun Hu* Biochemical Issues in Estimation of Cytosolic Free NAD/NADH Ratio. PLoS ONE | Volume 7 | Issue 5 | e34525, 2012.
Xuan Y & Hu X* Naturally-occurring shikonin analogues – A class of necrotptotic inducers that circumvent cancer drug resistance. Cancer Lett 2008, in press.
Lu Y, Xu X, Din Z, Liu Z, Zhang B, Yan Z, Sun J, Hu S*, Hu X* Complete genome of Phenylobacterium zucineum - a novel facultative intracellular bacterium isolated from human erythroleukemia cell line K562. BMC Genomics 9:368, 2008, e-pub ahead of print.
Hu X*, Xuan Y. Bypassing Cancer Drug resistance by activation of multiple death pathways – a proposal from the study circumventing cancer drug resistance by induction of necroptosis. Cancer Lett. 259：127-137, 2008.
Li L, Pan Q, Han W, Liu Z, Li L, Hu X*. Schisandrin B Prevents Doxorubicin-Induced Cardiotoxicity via Enhancing Glutathione Redox Cycling.Clin Cancer Res. 2007, 13(22):6753-60.
Hu X*, Han W, Li L. Targeting the weak point of cancer by induction of necroptosis.Autophagy. 2007,3(5):490-2.
Han W, Li L, Qiu S, Lu Q, Pan Q, Gu Y, Luo J, Hu X*. Shikonin circumvents cancer drug resistance by induction of a necroptotic death. Mol Cancer Ther. 2007, 6(5):1641-9.
Li L, Han W, Gu Y, Qiu S, Lu Q, Jin J, Luo J, Hu X*. Honokiol induces a necrotic cell death through the mitochondrial permeability transition pore. Cancer Res. 2007, 67(10):4894-903.
Zhang K, Han W, Zhang R, Xu X, Pan Q, Hu X*. Phenylobacterium zucineum sp. nov., a facultative intracellular bacterium isolated from a human erythroleukemia cell line K562. Syst Appl Microbiol. 2007, 30(3):207-12.
Pan Q, Lu Q, Zhang K, Hu X*. Dibenzocyclooctadiene – a class of novel inhibitors of P-glycoproteins. Cancer Chemother Pharmacol 58:99-106, 2006.
Li L, Pan Q, Sun M, Lu Q, Hu X* Dibenzocyclooctadiene-a class of novel inhibitors of multidrug resistance. Life Sciences. 80：741-748, 2007.
Sun M, Xu X, Lu Q, Pan Q, Hu X*. Schisandrin B – a Dual Inhibitor of P-glycoprotein and Multidrug Resistance-associated Protein 1. Cancer Lett, 246: 300-307, 2007.
Xu D, Lu Q, Hu X*. Downregulation of P-glycoprotein in expression in MDR brease cancer cell MCF-7/ADR by honokiol. Cancer Lett. 243:274-280, 2006.
Li L, Lu Q, Hu X*. Schisandrin B enhances doxorubicin-induced apoptosis of cancer cells but not normal cells. Biochem Pharmcol 71:584-595, 2006.
Pan Q, Wang T, Lu Q, Hu X*. Schisandrin B – a novel inhibitor of P-glycoprotein. Biochem Biophys Res Comm. 335:406-411, 2005.
Pan Q, Fang Y, Xu Y, Zhang K, Hu X*. Down-regulation of DNA polymerases kappa, eta, iota, and zeta in human lung, stomach, and colorectal cancers. Cancer Lett. 2005,217(2):139-47.
Chen YD, Zheng S, Yu JK, Hu X*. Artificial neural networks analysis of surface-enhanced laser desorption/ionization mass spectra of serum protein pattern distinguishes colorectal cancer from healthy population. Clin Cancer Res 2004, 10(24):8380-5.
Zhang K, Lu Q, Zhang Q, Hu X*. Regulation of activities of NK cells and CD4 expression in T cells by human HNP-1, -2, and -3. Biochem Biophys Res Comm. 2004, 323(2):437-44.
Pal A, Hu X, Zimniak P, Singh SV.Catalytic efficiencies of allelic variants of human glutathione S-transferase Pi in the glutathione conjugation of alpha, beta-unsaturated aldehydes.Cancer Lett. 154(1):39-43,2000.
Pal A, Desai DH, Amin S, Srivastava SK, Hu X, Herzog C, Zimniak P, Singh SV. Location of the epoxide function determines specificity of the allelic variants of human glutathione transferase Pi toward benzo[c]chrysene diol epoxide isomers. FEBS Lett. 486(2):163-6,2000.
Srivastava SK, Xia H, Pal A, Hu X, Guo J, Singh SV. Potentiation of benzo[a]pyrene-induced pulmonary and forestomach tumorigenesis in mice by D,L-buthionine-S,R-sulfoximine-mediated tissue glutathione depletion. Cancer Lett. 153(1-2):35-9,2000.
Srivastava SK, Hu X, Xia H, Awasthi S, Amin S, Singh SV. Metabolic fate of glutathione conjugate of benzo[a]pyrene-(7R,8S)-diol (9S,10R)-epoxide in human liver. Arch Biochem Biophys. 371(2):340-4,1999.
Pal A, Seidel A, Xia H, Hu X, Srivastava SK, Oesch F, Singh SV. Specificity of murine glutathione S-transferase isozymes in the glutathione conjugation of (-)-anti- and (+)-syn-stereoisomers of benzo[g]chrysene 11,12-diol 13,14-epoxide. Carcinogenesis. 20(10):1997-2001,1999.
Ji X, Blaszczyk J, Xiao B, O'Donnell R, Hu X, Herzog C, Singh SV, Zimniak P. Structure and function of residue 104 and water molecules in the xenobiotic substrate-binding site in human glutathione S-transferase P1-1.Biochemistry.38(32):10231-8, 1999.
Srivastava SK, Singhal SS, Hu X, Awasthi YC, Zimniak P, Singh SV. Differential catalytic efficiency of allelic variants of human glutathione S-transferase Pi in catalyzing the glutathione conjugation of thiotepa. Arch Biochem Biophys. 366(1):89-94,1999.
Srivastava SK, Hu X, Xia H, Pal A, Guo J, Orchard JL, Singh SV. Gender related differences in ATP-dependent transport of dinitrophenyl-glutathione conjugate across murine canalicular liver plasma membrane. FEBS Lett. 445(2-3):291-4,1999.
Hu X, Herzog C, Zimniak P, Singh SV. Differential protection against benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced DNA damage in HepG2 cells stably transfected with allelic variants of pi class human glutathione S-transferase. Cancer Res. 15;59(10):2358-62,1999.
Hu X, Xia H, Srivastava SK, Pal A, Awasthi YC, Zimniak P, Singh SV. Catalytic efficiencies of allelic variants of human glutathione S-transferase P1-1 toward carcinogenic anti-diol epoxides of benzo[c]phenanthrene and benzo[g]chrysene.Cancer Res. 8(23):5340-3,1998.
Singh SV, Hu X, Srivastava SK, Singh M, Xia H, Orchard JL, Zaren HA. Mechanism of inhibition of benzo[a]pyrene-induced forestomach cancer in mice by dietary curcumin. Carcinogenesis. 19(8):1357-60,1998.
Singh SV, Benson PJ, Hu X, Pal A, Xia H, Srivastava SK, Awasthi S, Zaren HA, Orchard JL, Awasthi YC. Gender-related differences in susceptibility of A/J mouse to benzo[a]pyrene-induced pulmonary and forestomach tumorigenesis. Cancer Lett. 128(2):197-204,1998.
Srivastava SK, Hu X, Xia H, Bleicher RJ, Zaren HA, Orchard JL, Awasthi S, Singh SV. ATP-dependent transport of glutathione conjugate of 7beta, 8alpha-dihydroxy-9alpha,10alpha-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene in murine hepatic canalicular plasma membrane vesicles. Biochem J 332 (3):799-805,1998.
Xia H, Pan SS, Hu X, Srivastava SK, Pal A, Singh SV. Cloning, expression, and biochemical characterization of a functionally novel alpha class glutathione S-transferase with exceptional activity in the glutathione conjugation of (+)-anti-7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene. Arch Biochem Biophys. 353(2):337-48,1998.
Singh SV, Pan SS, Srivastava SK, Xia H, Hu X, Zaren HA, Orchard JL. Differential induction of NAD(P)H:quinone oxidoreductase by anti-carcinogenic organosulfides from garlic. Biochem Biophys Res Commun. 244(3):917-20,1998.
Hu X, Pal A, Krzeminski J, Amin S, Awasthi YC, Zimniak P, Singh SV. Specificities of human glutathione S-transferase isozymes toward anti-diol epoxides of methylchrysenes.Carcinogenesis. 19(9):1685-9,1998.
Hu X, Seidel A, Frank H, Srivastava SK, Xia H, Pal A, Zheng S, Oesch F, Singh SV. Differential enantioselectivity of murine glutathione S-transferase isoenzymes in the glutathione conjugation of trans-3,4-dihydroxy-1, 2-oxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene stereoisomers.Arch Biochem Biophys. 358(1):40-8,1998.
Hu X, Benson PJ, Srivastava SK, Xia H, Bleicher RJ, Zaren HA, Awasthi S, Awasthi YC, Singh SV. Induction of glutathione S-transferase pi as a bioassay for the evaluation of potency of inhibitors of benzo(a)pyrene-induced cancer in a murine model. Int J Cancer. 73(6):897-902,1997.
Hu X, Singh SV. Differential catalytic efficiency and enantioselectivity of murine glutathione S-transferase isoenzymes in the glutathione conjugation of carcinogenic anti-diol epoxides of chrysene and benzo(g)chrysene. Arch Biochem Biophys. 345(2):318-24,1997.
Hu X, Xia H, Srivastava SK, Herzog C, Awasthi YC, Ji X, Zimniak P, Singh SV. Activity of four allelic forms of glutathione S-transferase hGSTP1-1 for diol epoxides of polycyclic aromatic hydrocarbons. Biochem Biophys Res Commun. 238(2):397-402,1997.
Hu X, Ji X, Srivastava SK, Xia H, Awasthi S, Nanduri B, Awasthi YC, Zimniak P, Singh SV. Mechanism of differential catalytic efficiency of two polymorphic forms of human glutathione S-transferase P1-1 in the glutathione conjugation of carcinogenic diol epoxide of chrysene. Arch Biochem Biophys. 345(1):32-8,1997.
Hu X, O'Donnell R, Srivastava SK, Xia H, Zimniak P, Nanduri B, Bleicher RJ, Awasthi S, Awasthi YC, Ji X, Singh SV.Active site architecture of polymorphic forms of human glutathione S-transferase P1-1 accounts for their enantioselectivity and disparate activity in the glutathione conjugation of 7beta,8alpha-dihydroxy-9alpha,10alpha-ox y-7,8,9,10-tetrahydrobenzo(a)pyrene. Biochem Biophys Res Commun. 235(2):424-8,1997.
Srivastava SK, Hu X, Xia H, Zaren HA, Chatterjee ML, Agarwal R, Singh SV. Mechanism of differential efficacy of garlic organosulfides in preventing benzo(a)pyrene-induced cancer in mice. Cancer Lett. 118(1):61-7,1997.
Xia H, Bleicher RJ, Hu X, Srivastava SK, Gupta V, Zaren HA, Singh SV. Characterization of a BMS-181174-resistant human bladder cancer cell line.Br J Cancer. 76(4):461-6,1997.
Hu X, Singh SV.Glutathione S-transferases of female A/J mouse lung and their induction by anticarcinogenic organosulfides from garlic. Arch Biochem Biophys. 340(2):279-86,1997.
Hu X, Srivastava SK, Xia H, Awasthi YC, Singh SV. An alpha class mouse glutathione S-transferase with exceptional catalytic efficiency in the conjugation of glutathione with 7beta, 8alpha-dihydroxy-9alpha, 10alpha-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene. J Biol Chem. 271(51):32684-8,1996.
Hu X, Benson PJ, Srivastava SK, Mack LM, Xia H, Gupta V, Zaren HA, Singh SV. Glutathione S-transferases of female A/J mouse liver and forestomach and their differential induction by anti-carcinogenic organosulfides from garlic.Arch Biochem Biophys. 336(2):199-214,1996.
Singh SV, Mohan RR, Agarwal R, Benson PJ, Hu X, Rudy MA, Xia H, Katoh A, Srivastava SK, Mukhtar H, Gupta V, Zaren HA. Novel anti-carcinogenic activity of an organosulfide from garlic: inhibition of H-RAS oncogene transformed tumor growth in vivo by diallyl disulfide is associated with inhibition of p21H-ras processing. Biochem Biophys Res Commun. 225(2):660-5,1996.
Hu X, Yang H, Pan QR, Zheng S. Does P-glycoprotein play a pivotal role in the drug resistance of an MDR variant, K562/Dox? Chemotherapy. 41(4):296-305,1995.
Hu X, Arnold WM, Zimmermann U. Alterations in the electrical properties of T and B lymphocyte membranes induced by mitogenic stimulation. Activation monitored by electro-rotation of single cells. Biochim Biophys Acta. 1021(2):191-200,1990.
The contribution of dehydrogenases to ROS generations in cancer cells and the biochemical mechanism. Funding Source: Natural Science Foundation of China.
Targeting intratumoral lactic acidosis for treating hepatocellular carcinoma. Funding Source: Zhejiang Provincial Department of Science and Technology.