Qi Chen , PhD, Assistant Professor

 

PhD, Department of Biochemistry, Sun Yet-sen University, China 2003

 

Research Interests

Basic and translational research in redox-related cancer medicine, with current focus on ascorbate (vitamin C, ascorbic acid) as pro-oxidant agent in cancer treatment.

High dose of intravenous ascorbate are widely used to treat cancer and infections by complementary and alternative medical practitioners. The efficacy and underlying scientific basis are poorly understood. On the other hand, little side effects were found in these treatments and in a Phase I clinical trial in cancer patients. Early observational studies and recent case reports show positive effect of ascorbate in cancer treatment. Furthermore, we’re still in lack of treatment options for a large number of cancers. Ascorbate as a low toxic and potentially effective agent may have great merits that worth investigation.   

Physiologic concentrations of ascorbate are tightly controlled through oral ingestion. Intravenous or intraperitoneal administrations can by-pass the tight control mechanism and achieve pharmacologic concentrations in millimolar range. In contrast to its normal anti-oxidant role, ascorbate in pharmacologic concentrations has pro-oxidant action in extravascular spaces, by generating ascorbate radical and hydrogen peroxide (H2O2) to tissues, with minimal formation of these compounds in blood. The pro-oxidant action of ascorbate induced selective cell death to some cancer cells but not to normal cells. An intraperitoneal ascorbate treatment regimen reduced tumor growth by 40~50% in three kinds of highly aggressive tumors in mouse models.

Dr. Chen accepted a position as Assistant Professor of Pharmacology at KUMC in November 2008. Before she joined KUMC, Dr. Chen completed the postdoctoral training in Laboratory of Molecular Clinical Nutrition in the National Institutes of Health (NIH). Dr. Chen’s lab is conducting researches focusing on the following respects: 1. Preclinical research of ascorbate treatment to cancers as adjunct to standard chemotherapeutics. 2. Basic and translational studies of ascorbate effects on tumor metastasis. 3. Role of host immune system in ascorbate treatment. 4. Mechanisms for the selectivity of ascorbate induced cytotoxicity. 5. Explore the role of ascorbate in infectious disease treatment.    

 Another research interested in Dr. Chen's lab is the candidate tumor suppressor gene PDSS2 (prenyl diphosphate synthase subunit 2). PDSS2 gene encodes an essential enzyme involved in the coenzyme Q10 (CoQ10) biosynthesis. CoQ10 is a vital electron carrier in the mitochondrial respiratory chain, and is one of the most potent lipophilic anitoxidants in all cell membranes. CoQ10 also takes part in pyrimidine nucleoside biosynthesis and may modulate cell apoptosis and the mitochondrial uncoupling protein. Thus PDSS2 may be important to modulate mitochondrial function and cell apoptosis. 

Selected Publications

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.

Frei B., Lawson S., Levine M., Chen Q., Espey M.G.. Reply to Borst: Randomized Clinical Trials of High-dose Intravenous Vitamin C in Cancer Patients are Warranted. Proc Natl Acad Sci USA. 2008; 105 : E95

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.

Chen Q., Cao R.H., Chen H.S., Hou X.R., Yan H.F., Zhou S.S., Peng W.L., Xu A.L. Antitumor and neurotoxic effects of novel harmine derivatives and structure-activity relationship analysis. Int. J Cancer. 2005; 114(5): 675-82.

Cao R.H., Peng W.L., Chen H.S., Hou X.R., Guan H.J., Chen Q., Ma Y, Xu A.L. A Synthesis and in vitro cytotoxic evaluation of 1,3-bisubstituted and 1,3,9-trisubstituted beta-carboline derivatives. Eur J Med Chem. 2005; 40(3): 249-57.

Cao R.H., Chen Q., Hou X.R., Chen H.S., Guan H.J., Ma Y., Peng W.L., Xu A.L. Synthesis, acute toxicities, and antitumor effects of novel 9-substituted beta-carboline derivatives. Bioorg Med Chem. 2004; 12(17): 4613-23.

Espey M.G., Chen Q., Sun A.Y., Kim H.S., Padayatty S., Wang Y., Tu H., Margolis S., Levine M.. Methodologies in the use, collection and analysis of ascorbate. In: Das DK, editor. Handbook of the methods for studying redox signaling. New York: Mary Ann Liebert; in press.

Contact Information

Qi Chen, Ph.D.
Assistant Professor
Department of Pharmacology, Toxicology and Therapeutics
The University of Kansas Medical Center
Room 4020 Smith East, MS 4016
3901 Rainbow Boulevard
Kansas City, Kansas 66160
Phone: (913) 588-3684
Fax: (913) 945- 6874
Email:qchen@kumc.edu

 

Updated 8/24/09