About the Lab
The Chan Lab's research interest includes the identification and purification of Anti-tumor agents from Chinese medicine. Herbal Medicine has been a common therapeutic approach for various illnesses, including cancerous tumors, for centuries. Dr. Chan found that the extract from the husk of a plant (Xanthoceras sorbifolia Bunge (Sapindaceae)) contain saponins that have anti-tumor effect. The active compound was purified and then chemically modified to remove unwanted side -effect. In vitro studies with these compounds show that it inhibits cancer cells’ growth. Application of this drug and the structure/function relationship is the focus of current research.
The general goal of this laboratory is to search for more novel drugs and identify its drug mechanism.
Publications
Liew, C. C. and Chan, P. K.: Identification of nonhistone chromatin protein sin chromatin subunits. Proc. Natl. Acad. Sci. 73: 3458 3462 (1976).
Chan, P. K. and Liew, C. C.: Identification of specific phosphoproteins in nuclease digested chromatin subunits. Can. J. Biochemistry 55: 847 855 (1977). PMID: 890579
Chan, P.K. and Liew, C.C.: Identification of nonhistone chromatin proteins in chromatin subunits (or mononucleosomes) devoid of histone H1. Can. J. Biochemistry 57: 666 672 (1979). PMID: 476514
Chan, P. K. and Liew, C. C.: Purification of a phosphoprotein from chromatin of rat liver. Biochem. J. 183: 147 156, (1979). PMID: 534478 PMCID: PMC1161483
Chan, P. K., Feyerabend, A., Busch, R. K., and Busch, H.: Identification and partial purification of tumor nucleolar antigens: Human tumor antigen 54/6.3. Cancer Res. 40: 3194 3201 (1980). PMID: 7000338
Chan, P. K., Frakes, R. L., Busch, R. K., and Busch, H.: Isolation and partial characterization of a nuclear antigen (68/6.3). From the Namalwa cell line (a Burkitt lymphoma). J. Cancer Res. & Clin. Oncol. 103: 7 16 (1982). PMID: 7076718
Busch, H., Busch, R. K., Chan, P. K., Choi, Y. C., Daskal, Y., Domae, N., Harmon, F., Kobayashi, K., Nohga, K., and Smetana, K.: Human tumor nucleolar antigens and nucleolar particles. Cancer Invest. 1: 25 40 (1983).
Takahashi, K., Chan, P. K., Busch, R. K., and Busch, H.: Identification and purification of Namalwa nuclear RNP antigen 52/5.3. J. Cancer Res. & Clin. Oncol. 105: 67 75 (1983). PMID: 6833342
Smetana, K., Gyorkey, F., Chan, P. K., Tan, E., and Busch, H.: Proliferating cell nuclear antigen (PCNA) and human malignant tumor nucleolar antigens (HMTNA) in nucleoli of human hematological malignancies. Blut 46: 133 141 (1983). PMID: 6337656
Deb, J. K., Chan, P. K., and Busch, H.: A 38,000 dalton antigen found in Namalwa cells induced by Newcastle disease virus. Proc. Soc. Exptl. Biol. & Med. 172: 535 542 (1983). PMID: 6682552
Chan, P. K., Frakes, R., Tan, E. M., Brattain, M. G., Smetana, K., and Busch, H.: Indirect immunofluorescence studies of proliferating cell nuclear antigen in nucleoli of human tumor and normal tissues. Cancer Res. 43: 3770 3777, (1983). PMID: 6134581
Busch, R. K., Chan, P. K., and Busch, H.: Actinomycin D inhibition of monoclonal antibody binding to nucleolar phosphoprotein 37/5.2 (B23). Life Sci. 35: 1777 1785 (1984). PMID: 6207410
Chan, P. K., Aldrich, M., Tan, E. M., and Busch, H.: Detec tion of a 140 kDa nucleolar protein with an anti PCNA auto antibody. Cell Biol. Intl. Repts. 9: 61 68 (1985). PMID: 2858268
Chan, P. K., Aldrich, M., and Busch, H.: Alterations in immunolocalization of the phosphoprotein B23 in HeLa cells during serum starvation. Exptl. Cell Res. 161: 101 110, (1985). PMID: 2414117
Yung, B. Y. M., Busch, R. K., Busch, H., Mauger, A. B., and Chan, P. K.: Effects of actinomycin D analogs on nucleolar phosphoproteins B23 (37 kD/pI 5.1). Biochemical Pharm. 34: 4059 4063 (1985). PMID: 2415133
Yung, B. Y. M., Busch, H., and Chan, P. K.: Translocation of nucleolar phosphoprotein B23 (37 kD/pI 5.1) induced by selective inhibitors of ribosome synthesis. Biochim. Biophys. Acta 826: 167 173 (1985). PMID: 3907710
Chan, P. K., Aldrich, M., Cook, R. G., and Busch, H.: Amino acid sequence of protein B23 phosphorylation site. J. Biol. Chem. 261: 1868 1872 (1986). PMID: 3944116
Yung, B. Y. M., Busch, H. and Chan, P. K.: Effects of luzopeptins on protein B23 translocation and rRNA synthesis. Cancer Res. 46: 922 925 (1986). PMID: 3940652
Chan, P.K., Chan, W. Y., Yung, B. Y. M., Cook, R.G, Aldrich, M.B., Ku, D., Goldknopf, I.L., and Busch, H.: Amino acid sequence of a specific antigenic peptide of protein B23. J. Biol. Chem. 261: 14335 14341 (1986). PMID: 2429957
Yung, B. Y M. and Chan, P.K.: Identification and characterization of an hexameric form of nucleolar phosphoprotein B23 (M.W./pI=37KD/5.1). Biochim. Biophys. Acta. 925: 74 82. (1987). PMID: 3593769
Chan, P.K., Aldrich, M.B.,and Yung, B. Y M.: Studies of nucleolar protein B23 translocation after doxorubicin treatment in murine tumor cells. Cancer Res. 47: 3798 3801, (1987). PMID: 3593769
Feuerstein, N., Chan, P.K., and Mond, J.J.: Identification of numatrin, the nuclear matrix protein associated with induction of mitogenesis, as the nucleolar protein B23. Implication for the role of the nucleolus in early transduction of mitogenic signals. J. Biol. Chem. 263: 10608 10612 (1988). PMID: 3392030
Chan, W.Y., Tease, L.A., Borjigin, J., Chan, P.K., Rennert O.M., Srinivasan, B., Shupert. W.L., and Cook, R.G.: Pregnancy-specific ß1 glycoprotein mRNA is present in placental as well as non-placental tissues. Human Reproduction, 3: 677-685, (1988). PMID: 3262622
Chan, P.K., Aldrich, M.B., and Chakrabarty, S.: Assessment of tumor cell sensitivity to mitomycin C by "B23 translocation" assay. Cancer letters, 40: 143 149, (1988). PMID: 3133107
Chan, W.Y., Liu, Q.R., Borjigin, J., Busch, H., Rennert, O.R., Tease. L.A., and Chan, P.K.: Characterization of the cDNA encoding human nucleophosmin and studies of its role in normal and abnormal growth. Biochemistry, 28: 1033 1039, (1989). PMID: 2713355
Sweet, P., Chan, P.K. and Slater, L.M.: Cyclosporin A and Verapamil enhancement of daunorubicin produced nucleolar protein B23 translocation in daunorubicin resistant and sensitive tumor cells. Cancer Res. 49: 677 680, (1989). PMID: 2910487
Chan, P.K.: Cross linkage of nucleophosmin in tumor cells by Nitrogen Mustard. Cancer Res. 49:3271 3275, (1989). PMID: 2720680
Liu, Q. R. and Chan, P.K.: Identification of a long stretch of homopurine · homopyrimidine sequence in a cluster of retroposons in the human genome. J. Molecular Biology, 212:453-459, (1990). PMID: 2157848
Yung, B. Y-M., Bor, M. S., Chan, P.K.: Short exposure of actinomycin D induced "reversible" translocation of protein B23, inhibition of cell growth and RNA synthesis. Cancer Res. 50: 5987-5991 (1990). PMID: 1697505
Chan, P.K., Liu, Q.R. and Durban, E.: The major phosphorylation site of nucleophosmin (B23) is phosphorylated by a nuclear kinase II. Biochemical Journal 270:549-522 (1990). PMID: 2400401
Liu, Q-R and Chan, P.K.: Formation of nucleophosmin/B23 oligomers requires both the amino- and the carboxyl-terminal domains of the protein. Eur. J. Biochem. 200:715-721, (1991). PMID: 1915343
Slater, L.M., Sweet, P., Hsu, T.C. and Chan, P.K.: Novel nucleolar and nuclear morphology in a vincristine dependent human leukemia cell line (L100). Experimental Cell Research, 198:170-174 (1992). PMID: 1727053
Finch, R.A. and Chan, P.K.: Studies of actinomycin D induced B23-translocation in P388D1 cells implanted in DBA/2 mice. Oncology, 49:223-226 (1992). PMID: 1495750
Yung, B. Y-M., Hui, E. K-W. and Chan, P.K.: Protein B23 (M.W./pI = 37 kD/5.1) is the only major protein extracted from HeLa nucleoli with 3M Urea. Life Science, 51:915-920 (1992). PMID: 1518368
Chan, P.K. Characterization and cellular localization of nucleophosmin/B23 in HeLa cells treated with selected cytotoxic agents (studies of B23-translocation mechanism). Experimental Cell Research, 203: 174-181 (1992) PMID: 1426041
Liu, Q. R. and Chan, P.K. Characterization of seven processed pseudogenes of nucleophosmin/B23 in the human genome. DNA and Cell Biology, 12:149-156, (1993). PMID: 8471164
Lui, C. P., Chan, P.K., Fung, K.P., Choy, Y.M. and Lee, C.Y. Effects of hyperthermia on the nucleolar proteins in tumor cells. Cancer Letters 70:129-139,(1993)
Finch, R.A., Revankar, G.R. and Chan, P.K. Nucleolar localization of nucleophosmin/B23 requires GTP. J. Biol. Chem. 268:5823-5827, (1993). PMID: 8095498
Valdez, B.C., Perlaky, L., Henning, D., Saijo, Y., Chan, P.K. and Busch, H. Identification of the nuclear and nucleolar localization signals of the protein p120. Interaction with translocation protein B23. J. Biol. Chem. 269:23776-23783, (1994). PMID: 8089149
Chan, P.K. and Fung Y. Chan. Nucleophosmin/B23 (NPM) oligomer is a major and stable entity in HeLa cells. Biochim. Biophys. Acta , 1262: 37-42, (1995). PMID: 7772597
Finch, R.A., D. Chang and Chan, P.K. GTP gamma S restores nucleophosmin (NPM) localization to nucleoli of GTP-depleted HeLa cells. Molecular and Cellular Biochemistry, 146: 171-178, (1995). PMID: 7565647
Chan, P.K., Qi, Y , Amley, J. and Koller, C.A. Quantitation of the NPM-translocation using imaging analysis. Cancer Letters 100:191-197, (1996) PMID: 8620441
Finch, A. R. and Chan, P.K. ATP depletion affects NPM translocation and exportation of rRNA from nuclei. Biochemical Biophysical Research Communications, 222: 553-558, (1996). PMID: 8670243
Chan, P.K., Chan, F.Y., Morris, S.W. and Xie, Z. Isolation and characterization of the human nucleophosmin/B23 (NPM) gene: identification of the YY1 binding site at the 5’ enhancer region. Nucleic Acid Research, 25:1225-1232, (1997). PMID: 9092633
Finch, A.R., Revankar, G.A. and Chan, P.K. Structural and functional relationships of toyocamycin on NPM-translocation. Anti-Cancer Drug Design, 12: 205-215, (1997). PMID: 9154111
Smetana, K., Chan, P.K., Jiraskova, I and Busch, H.: Nucleolar coefficient and cytochemistry of human blood monocytes. Life Sciences 60: 2199-2205, (1997). PMID: 9188763
Smetana, K., Jiraskova, I., Turek, P., Chan, P.K. and Busch, H. A contribution to the incidence of nucleoli in normal human blood monocytes. Haematologica, 82:138-142, (1997). PMID: 9175314
Luthra, R., Pugh, W.C., Waasdorp, M., Morris, W., Cabanillas, F., Chan, P.K. and Sarris, H.: Mapping of genomic t(2;5)(p23;q35) break points in patients with anaplastic large cell lymphoma by sequencing long-range PCR products. Hematopathology and Molecular Hematology, 11: 173-183 (1998). PMID: 9844824
Zatsepina, O.V., Rousselet, A., Chan, P.K., Olson, M.O., Jordan, E.G., Bornens, M.: The nucleolar phosphoprotein B23 redistributes in part to the spindle poles during mitosis. J Cell Sci. 112: 455-466, (1999). PMID: 9914158
Subong, E.N.P., Shue, M.J., Epstein, J.I., Briggman, J.V., Chan, P.K. and Partin, A.W.: Monoclonal antibody to prostate cancer nuclear matrix protein (PRO:4-216) recognizes nucleophosmin/B23. The Prostate 39:298-304 (1999). PMID: 10344220
Chan, P.K. and Chan, F.Y.: A study of correlation between NPM-translocation and apoptosis in cells induced by daunomycin. Biochemical Pharmacology, 57: 1265-1273, (1999). PMID: 10230770
Chan, P.K., Bloom, D.A. and Hoang, T.T.: The N-terminal half of NPM dissociates from nucleoli of HeLa cells after anticancer drug-treatments. Biochemical Biophysical Research Communications, 264:305-309, (1999). PMID: 10527882
Okuda, M., Horn, H.F., Tarapore, P. Tokuyama, Y., Smulian, A.G., Chan, P.K., Knudsen, E.S., Hofmann, I.A., Snyder, J.D., Bove, K.E and Fukasawa, K.: Nucleophosmin/B23 is a target of CDK2/Cyclin E in centrosome duplication. Cell, 103:127-140, (2000). PMID: 11051553
Chan, P.K.: Inhibition of tumor growth in vitro by the extract of Fagopyrum cymosum (Fago-c). Life Sciences 72:1851-1858, (2003). PMID: 12586222
Smetana, K., Chan, P.K., Marinov, Y., Soucek, J., Hrkal, Z. and Busch, H.: A short note on the nucleolar size and density in apoptotic leukemic granulocytic precursors (HL-60 cells). Life Sciences 75:791-796, (2004). PMID: 15183072
Ahn JY, Liu X, Cheng D, Peng J, Chan PK, Wade PA, Ye K.: Nucleophosmin/B23, a nuclear PI(3,4,5)P(3) receptor, mediates the antiapoptotic actions of NGF by inhibiting CAD. Mol Cell. 2005 May 13;18(4):435-45. PMID: 15893727
Chan, PK.: Acylation with diangeloyl groups at C21-22 positions in triterpenoid saponins is essential for cytotoxicity towards tumor cells. Biochem Pharmacol. 73:341-350 (2007). PMID: 17092489
Chan PK, Zhao M, Che CT, Mak E. Cytotoxic acylated triterpene saponins from the husks of Xanthoceras sorbifolia, J. Nat. Prod. 2008;71:1247-50. B. PMID: 18549275
Chan, P.K. and Liu, Q.R.: Interaction of nucleophosmin (protein B23) with cytotoxic drugs. Proc. Am. Cancer Res. 31:396, 1990.
Finch, R. and Chan, P.K.: Studies of B23-translocation in P388D1 cells implanted in DBA/2 mice. Proc. Am. Cancer Res. 32: 379, 1991.
Slater, L., Sweet, P. and Chan, P.K.: Multidrug resistant acute lymphatic leukemia (ALL) with vincristine (VCR) dependence and novel nucleolar and nuclear morphology. Proc. Am. Cancer Res. 32: 362, 1991.
Finch, R.A., Revankar, G.R. and Chan, P.K.: Studies of structural and functional relationship of adenosine analogs on B23-translocation. Proc. Am. Cancer Res. 33:541 (1992)
Leung, M.F., Sartorelli, A.C., Sweet, P., Chan, P.K., and Slater, L.M.: Microtubule-dependent nuclear morphology in the multidrug resistant human leukemia cell line L100. Proc. Am. Cancer. Res. 33:461 (1992).
Finch, R.A. and Chan, P.K.: Effects of ribavirin on nucleolar proteins: nucleolar localization of nucleophosmin/B23 requires GTP. The FASEB Journal 7:A691 (1993)
Chan, P.K. and Chan, F.Y. Localization of nucleophosmin/B23 (NPM) and the pleomorphic structure of nucleoli in HeLa cells are reversibly abolished by camptothecin, independent of protein synthesis. Cold Spring Harbor Lab. Symposium on Ribosome synthesis and Nucleolar Function, p26, 1994.
Chan, P.K., Qi., Y., and Aldrich, M. Effect of mithramycin on cellular localization of nucleophosmin/B23 (NPM). Proc. Am. Cancer. Res. 36:349 (1995)
Chan, P.K. and Chan, F.Y. Nucleophosmin/B23 (NPM) oligomer is a major and stable entity in HeLa cells. Proc. Am. Cancer. Res. 36:507 (1995)
Chan, P.K., Chan, F.Y., Leng, X.H., Morris, S.W. and Liu, Q.R. Isolation and characterization of the human NPM gene. Proc. Am. Cancer. Res. 37:515 (1996)
Chan, P.K.: Nucleophosmin/B23 (NPM), a major nucleolar protein: (a) gene structure and expression, (b) NPM-translocation and apoptosis. The Wilhelm Bernhard workshop: 15th International Workshop on the Cell nucleus, Lac-Delage, Quebec, Canada. p28, (1998).
Chan, P.K. and Chan, F.Y. A simple assay for determining the drug-effect of daunomycin in cancer cells: Direct correlation of NPM-translocation with apoptosis induced by daunomycin. Proc. Am. Cancer. Res. 39:429 (1998)
Chan, P.K. and Bloom, D.A. The N-terminal domain(s) of NPM is essential for drug-induced NPM-translocation. Proc. Am. Cancer. Res. 40:15 (1999)
Chan, P.K. and Chan, J.T. Changes in protein profiles of fluoride-treated MC3T3 cells. Proc. Am. Asso. Dental Res. (2003)
Chen, C.H., Chan, P.K., King, I. and Belcourt, M.F. Identification of critical components for anti-tumor activity of attenuated Salmonella. Proc. Am. Cancer. Res. 45: (2004)
Chan, PK and Mak, E: A novel compound isolated from Xanthoceras sorbifolia inhibits ovarian cancer: Identification of diangeloyl groups in saponin essential for anti-tumor activity. Proc Am. Asso. Cancer Res, 47: 452-453 (2006), Abstract #1919.
Chan, PK and Wong KK: Anti-tumor activities of a saponin (Y3) on ovarian cancer cells. Proc Am. Asso. Cancer Res, 50:116 (2009), Abstract #167. C. Review Articles
Lab Projects
Pacific Arrow/Data Prospect Company Ltd. Hong Kong (4/17 -3/20)
“Determine the cellular effects of herbal drug X”
P.I. 71% efforts, total cost $348,000
Pacific Arrow/Data Prospect Company Ltd. Hong Kong (4/14 -3/17)
“Determine the cellular effects of herbal drug X”
P.I. 70% efforts, total cost $345,600
Pacific Arrow/Data Prospect Company Ltd. Hong Kong (4/11 -3/14)
“Determine the cellular effects of herbal drug X”
P.I. 70% efforts, total cost $333,445
Pacific Arrow/Data Prospect Company Ltd. Hong Kong (4/08 -3/11)
“Determine the cellular effects of herbal drug X”
P.I. 70% efforts, total cost $299,487
Data Prospect Company Ltd. Hong Kong (4/07 -3/08)
“Determine the cellular effects of herbal drug X”
P.I. 70% efforts, total cost $90,000
Data Prospect Company Ltd. Hong Kong (4/06 -3/07)
“Determine the cellular effects of herbal drug X”
P.I. 60% efforts, total cost $80,000
Data Prospect Company Ltd. Hong Kong (4/05 -3/06)
“Determine the cellular effects of herbal drug X”
P.I. 50% efforts, total cost $60,000
ELSA U. Pardee Foundation (5/03 – 6/05)
“Isolation of the synergistic ingredient for cancer chemotherapy in the herbal drug Fago-c”.
P.I. 32% efforts, total cost $75,000
Data Prospect Company Ltd. Hong Kong (10/03 -4/05)
“Determine the cellular effects of herbal drug X”
P.I. 30% efforts, total cost $60,000
VION Pharmaceuticals, Inc. (2001- 2003)
“Protein expression profiles of attenuated tumor-targeting Salmonella”
P.I., 10% effort, total cost $45,000
NIH R43 CA096292 (2/1/03 – 7/31/03)
(SBIR phase-1, VION Pharmaceuticals Inc.)
“Identification of Tumoricidal Components in Salmonella”
Co-PI, 30% efforts, total cost $49,261
International Herbal Pharmaceuticals, Corp. (2002)
“Studies of the molecular targets of fagopyrum cymosum”
P.I., 30% efforts, total cost $109,746
NIH 5 R01 CA 42476, (3/94-2/97, extended to 2/99)
"Drug Effects on Function of Phosphoprotein B23"
P.I., 60% effort, direct cost $351,592/3 years
Texas Higher Edu. Coordinating Board, ATP (1/94-8/96)
"An in vitro drug effect assay for cancer patients"
P.I., 20% effort, direct cost $163,567/2 years
NIH 5 R01 CA 42476, (4/89-3/94)
"Drug Effects on Function of Phosphoprotein B23"
P.I., 45% effort, direct cost $532,205/5 years
NIH 5 RO1 CA 42476, (4/86-3/89)
"Drug Effects on Function of Phosphoprotein B23"
P.I., 25% effort, direct cost $178,688/3 years
NIH 5 PO1 CA 10893, (8/85-7/87)
"Pharmacological Studies of Luzopeptin and Echinomycin.
Co-PI, 10% effort, direct cost $25,747/year
