Ph.D., Department of Biochemistry, Sun Yet-sen University, China 2003
Postdoctoral Fellow, NIDDK / NIH , 2008
Our interest is in basic and translational research in natural products as inhibitors of cancer cell epithelial-mesenchymal transition (EMT), and cancer stem cells (CSCs).
One of our current research is in the efficacy and mechanism of ascorbate (Vitamin C, ascorbic acid) as pro-oxidant agent in cancer treatment. High dose intravenous ascorbate (IVC) is widely used by oncology patients independent of their oncologists, with anecdotal efficacy. The underlying scientific basis is poorly understood. On the other hand, IVC is very well tolerated, providing a big advantage for adding this non-toxic and potentially effective agent to current chemotherapies. Before IVC can be clinically tested as cancer therapy, there is a critical need to understand its mechanism(s) of action.
Earlier studies from our group have found that ascorbate concentrations are tightly controlled through oral ingestion under physiological conditions. In contrast, intravenous or intraperitoneal administrations can by-pass the tight control and achieve pharmacologic concentrations in millimolar range. At these concentrations, ascorbate can generate ascorbate radical and hydrogen peroxide (H2O2) through local auto-oxidation, casting sever oxidative stress to tumor cells without increasing systematic oxidative stress. In another word, ascorbate acts as a pro-drug for peroxide delivery to selectively kill tumor cells.
In continuous and expanding of these researches, we are conducting basic research as well as early phase clinical trials using IVC as anti-cancer agent. My lab is actively conducting researches focusing on the following respects: 1. Mechanisms of selective cytotoxicity of ascorbate to cancer cells, with focus on DNA damage and metabolic stress induced by ascorbate. 2. The effect and mechanism of ascorbate on tumor metastasis, with focus on cancer cell EMT inhibition, and CSC inhibition. 3. Role of host immune system in ascorbate treatment. 4. Combination of ascorbate treatment with standard chemotherapeutic drugs, based on the mechanism studies.
My lab has other projects ongoing studying natural products in treatment and prevention of pancreatic cancer and ovarian cancer, with focus on histone deacetylase inhibitors (HDACi). We also have high-throughput screening project looking for novel EMT inhibitors for discovery of inhibitors for pancreatic cancer stem cells.
Selected Journal Papers
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. (Featured in PNAS papers of the week.)
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., 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. (Featured in PNAS papers of the week. Had a commentary article. One of the most downloaded paper in PNAS August 2008.)
Padayatty S., Sun A.Y., Chen Q., Norris J., Drisko J., Levine M.. Vitamin C: Intravenous Use by Complementary and Alternative Medicine Practitioners and Adverse Effects. PLos One. 2010; 5(7): e11414. doi:10.1371/journal.pone.0011414.
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. (Had a commentary article in FRBM.)
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):681-7.
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. Anticancer Drugs; 2012; 23(4):437-44. doi: 10.1097/CAD.0b013e32834fd01f.
Kong B, Csanaky IL, Aleksunes LM, Patni M, Chen Q, Ma X, Jaeschke H, Weir S, Broward M, Klaassen CD, Guo GL. Gender-specific reduction of hepatic Mrp2 expression by high-fat diet protects female mice from ANIT toxicity. Toxicology and Applied Pharmacology; 2012; 261(2):189-95.
Chen Q. Vitamin C in Cancer Treatment: Where Pharmacokinetics Speaks. J Drug Metab Toxicol. 2012; 3:3. In press.
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; 2012. In revision.
Chen P, Yu J, Knecht J, Chen Q. Decrease of PDSS2 expression, a novel tumor suppressor, in non-small cell lung cancer. Cancer Epidemiology. 2012. In revision.
Selected Meeting Abstracts
Chen Q., Espey M., Lee J.,Zhang L., Krishna M., Sun A., Pooput C., Kirk K., Choyke P., Buettner G., Shacter E., Levine M. Ascorbic acid in pharmacologic concentrations: a pro-drug for selective delivery of ascorbate radical and hydrogen peroxide to the extravascular space in vivo. Free Radic. Biol. Med. 2006; 41(S1): S64. (FRBM Society Travel Award winner)
Chen Q., Sun A., Espey M., Levine M. Ascorbic acid as a pro-oxidant therapeutic agent in cancer. Free Radic. Biol. Med. 2007; 43(S1): S110 (FRBM Society Travel Award winner)
Chen Q., Pharmacologic Ascorbate as a pro-oxidant: An Unanticipated Role in Cancer Treatment. American College for Advancement in Medicine 2008 Fall Conference, Las Vegas, NV. Oct 8-10, 2008. (Invited speech)
Chen Q, Drisko J, Espey MG, Levine M. Pharmacologic Ascorbate as a pro-oxidant: An Unanticipated Role in Cancer Treatment. The 11th Conference of International Society of Integrative Medicine, Tokyo, Japan, July 12-14, 2010. (Invited speech)
Chen Q, Drisko J, Espey MG, Levine M. Pharmacologic Ascorbate as a pro-oxidant: Role in Cancer Treatment. The 2nd International Annual Riordan IVC Symposium, Wichita, Kansas, Oct. 8-9, 2010. (Invited speech)
Ma Y, Drisko J, Polireddy K, Chen Q. Synergistic effects of ascorbatewith carboplatin against human ovarian cancer in vitro and in vivo. Society for Integrative Oncology 8th International Conference, Cleveland, Ohio, Nov. 10-12, 2011. (Chosen for oral presentation. Young Investigator Award to Ma Y, postdoc in Chen Lab)
Chen P, Chalmers B, Drisko J, Chen Q. Pharmacologic ascorbate synergizes with gemcitabine in pre-clinical models of pancreatic cancer. Society for Integrative Oncology 8th International Conference, Cleveland, Ohio, Nov. 10-12, 2011. (Chosen for oral presentation)
Sullivan G, Chen Q, Chen P, Chapman J, Levine M, Drisko J. Prospective randomized phase I/IIa pilot trial to assess safety and benefit administering high-dose intravenous ascorbate in combination with chemotherapy in newly diagnosed advanced stage III or Stage IV ovarian cancer. Society for Integrative Oncology 8th International Conference, Cleveland, Ohio, Nov. 10-12, 2011. (Chosen for oral presentation)
Yu J, Drisko J, Chen Q. Activity of Pao Pereeira and Rauwolfia vomitoria extracts against ovarian cancer and pancreatic cancer. Society for Integrative Oncology 9th International Conference. Albuquerque, NM. Oct 8-10, 2012. (Chosen for oral presentation)
Polireddy K, Yu J, Drisko J, Chen Q. Ascorbate inhibits tumor invasion and metastasis by inhibiting epithelial mesenchymal transition (EMT) of PANC-1 cells. Society for Integrative Oncology 9th International Conference. Albuquerque, NM. Oct 8-10, 2012. (Chosen for oral presentation at the Best of SIO session.Early Career Award to Polireddy K, graduate student in Chen Lab)
Levine M, Padayatty S., Wang Y.H., Corpe C. P., Lee J., Wang J., Chen Q., Zhang L.Q.. Vitamin C. In Biochemical, Physiological, Molecular Aspects of Human Nutrition (2nd edition). Stipanuk M. Saunders, Elsevier Inc. St. Louis MO, 2006; Chapter 27 pp760-96.Espey M.G., Chen Q., Sun A.Y., Kim H.S., Padayatty S., Wang Y., Tu H., Margolis S., Levine M.. Ascorbate Methodologies and Considerations. In: Das DK, editor.Handbook of the methods for studying redox signaling. New York: Mary Ann Liebert; 2009; pp 24-31.
Qi Chen, Ph.D.
G001 Wahl East; MS-1018
3901 Rainbow Blvd.
Kansas City, KS 66160
F: (913) 588-7501