Qi Chen, PhD
Ph.D., Department of Biochemistry, Sun Yet-sen University, China 2003
Postdoctoral Fellow, NIDDK / NIH , 2008
Basic and translational research in cancer medicine, cancer drug development and mechanism studies with small molecules, with current focus on cancer epithelial-mesenchymal transition and cancer stem cells.
High dose intravenoud ascorate (vitamin C, ascorbic acid) as a cancer treatment. High dose of intravenous ascorbate (IVC) is a popular treatment for cancer in the world of complementary and alternative medicine (CAM), with profound safety and anicdotal clinical benefits. In previous studies, we found intravenous administration of ascorbate by passed its physiological "tight control" of obsoption for oral doses, and reached concentrations in millimolars in the body. These pharmacologic concentrations exerted a pro-oxidant action, in contrast to its normal anti-oxidant role, by generating ascorbate radical and hydrogen peroxide (H2O2) to tissues, with minimal formation of ROS in blood. The pro-oxidant action of ascorbate selectively kills cancer cells but spares normal cells, by mechanisms not understood yet. A number of animals studies all over the world have confimed our discovery that ascorbate treatment reduced tumor growth of verious cancers.
We have conducted a Phase I/IIa trial in ovarian cancer patients, adding IVC to the standard carboplatin/paclitxol chemotherapy. IVC significantly decreased chemo-associated toxicities in patients, and suggested prolonged disease relapes time. In continuous and expanding of these researches, my lab is actively conducting researches focusing on the following respects: 1. Mechanisms of selective cytotoxicity of ascorbate to cancer cells, with focus on cancer metabolism based on Warburg Effect. 2. The effect and mechanism of ascorbate on tumor metastasis, with focus on cancer cell EMT inhibition, and cancer stem cell inhibition. 3. Influences of ascorbate to the cancer microenvironment, in terms of metastasis inhibition.
My lab has other projects ongoing studying natural products in treatment and prevention of pancreatic cancer and ovarian cancer. We also have high-throughput screening project looking for novel EMT inhibitors and inhibitors for pancreatic cancer stem cells.
Ma Y, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q. High-dose parenteral ascorbate enchanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Science Translational Medicine. 2014, 6, 222ra18.
Yu J, Chen Q. Antitumor activities of Rauwolfia vomitoria extract and potentiation of gemcitabine effects against pancreatic cancer. Integrative Cancer Therapies. 2014, 13 (3): 217-25.
Chen P, Zhang Y, Polireddy K, Chen Q. The tumor-suppressing activity of the prenyl diphosphate synthase subunit 2 gene in lung cancer cells. Anti-Cancer Drugs. 2014, 25(7): 790-8.
Yu J, Drisko J, Chen Q. Inhibition of pancreatic cancer and potentiation of gemcitabine effects by extract of Pao Pereira. Oncology Report. 2013, 30 (1): 149-56.
Chen P, Yu J, Knecht J, Chen Q. Decrease of PDSS2 expression, a novel tumor suppressor, in non-small cell lung cancer. Cancer Epidemiology. 2013; 37: 166-71.
Ma Y, Sullivan G, Schrick E, Choi IY, He Z, Lierman J, Lee P, Drisko J, Chen Q. A convenient method for measuring blood ascorbate concentrations in patients receiving high-dose intravenous ascorbate. Journal of the American College of Nutrition; 2013, 32(3): 187-93.
Chen P, Yu J, Chalmers B, Drisko J, Yang J, Li BY, Chen Q. Pharmacological Ascorbate Induces Cytotoxicity in Prostate Cancer Cells through ATP Depletion and Induction of Autophagy. Anti-Cancer Drugs; 2012; 23(4):437-44.
Espey MG, Chen P, Chalmers B, Drisko J, Sun AY, Levine M, Chen Q. Pharmacologic ascorbate synergizes with gemcitabine in pre-clinical models of pancreatic cancer. Free Radic Biol Med. 2011; 50(11): 1610-9.
Chen P, Stone J, Sullivan G, Drisko J, Chen Q. Supplementary glutathione counteracts with pharmacologic ascorbate in pre-clinical cancer models. Free Radic Biol Med. 2011; 51(3):681
Chen Q., Espey M.G., Sun A.Y., Pooput C., Kirk K.L., Krishna M.C., Khosh D.B., Drisko J.A., Levine M.. Pharmacologic doses of ascorbate act as a pro-oxidant and decrease growth of aggressive tumor xenografts in mice. Proc Natl Acad Sci USA. 2008; 105 (32): 11105-9.
Chen Q., Espey M.G., Sun A.Y., Lee J.H., Cherukuri M.K., Shacter E, Choyke P.L., Pooput C., Kirk K.L., Buettner G.R., Levine M. Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci USA. 2007; 104(21): 8749-54.
Chen Q., Espey M.G., Krishna M.C., Mitchell J.B., Corpe C.P., Buettner G.R., Shacter E., Levine M. Ascorbic acid at pharmacologic concentrations selectively kills cancer cells: ascorbic acid as a pro-drug for hydrogen peroxide delivery to tissues. Proc Natl Acad Sci USA. 2005; 102(38): 13604-9.