Leng Chee Chang, PhD

Leng Chee Chang, PhD

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Associate Professor, Natural Products & Experimental Therapeutics Program, University of Hawaiʻi Cancer Center

Academic Appointment(s):
Associate Professor, College of Pharmacy, University of Hawaiʻi Hilo

Degree(s):
Ph.D. (Natural Product Chemistry), College of Pharmacy, University of Illinois at Chicago, Chicago, IL
MS (Organic Chemistry), National University of Malaysia, Sabah, Malaysia

Research Focus

The research interests of Dr. Chang include the isolation, identification, and biological evaluation of compounds from higher plant and microbial origin. Her long-term goals is to discover natural products as cancer chemotherapeutic agent, by which promising bioactive compounds may serve as lead compounds for drug design. Her work on targeting the aberrant Signal Transducer and activator of Transcription (STAT)3 (collaborator, Professor James Turkson) and NF-B (collaborator, Professor John M. Pezzuto) pathways. The critical role for persistently-active STAT3 in tumorigenesis has been reported in a variety of human cancers. The significance of aberrantly-active STAT3 and NF-B molecular targets and their links with cancer have been reported in literature. In the context of the reported cross-talk between NF-B and STAT3 in tumorigenesis, pSTAT3 promotes the nuclear accumulation of NF-B RelA (p65).

Currently, Dr. Chang's lab is studying Vernonia cinerea (Vc) and Physalis peruviana (poha berry). The poha berries are eaten fresh or used in making jam. The crude organic extract from the whole poha plant has anti-inflammatory activity in vitro, having shown inhibition of MDA-MB-231 breast cancer cells. The identification of bioactive lead compounds from VC and poha is underway. Their preliminary results showed that Vernonia cinerea (Vc)-derived extracts and chemical entities selectively inhibited the viability of U251 MG glioblastoma cells, through mechanisms that included the inhibition of aberrantly-active Stat3. Treatment with several pure sesquiterpene lactones (SL)derived from Vc showed significant pY705Stat3 inhibition in U251MG cells, with IC50 values of 1.1-2.97 M, while the other sesquiterpene lactones analogs were inactive.

Current study is focused on the SL structure-activity relationships, and to determine the molecular mechanism for the inhibition of Stat3 activity and the role of Stat3 in the antitumor cell effects. The long-term goal of Dr. Chang's lab is to discover safe and efficacious natural product-based inhibitors of aberrantly-active Stat3 for treating glioblastoma multiforme.

Selected Publications

Acuña, U.M., Fatima, N., Ahmed, S., Chang, L.C., Carcache de Blanco, E.J. (2013). Apoptotic Effect of Wortmannolone on Cancer Cells through Potent ROS Induction. International J. Cancer Research. Accepted.

I-Haq, I., Youn, U.J., Chai, X.Y., Park, E.J., Kondratyuk, T.P., Simmons, C. J., Borris, R.P., Mirza, B., Pezzuto, J.M., Chang, L.C. (2013). Biologically active withanolides from Withania coagulans. J. Nat. Prod. 76, 22-8.

Youn, U.J., Park, E.J., Kondratyuk, T.P., Simmons, C. J., Borris, R.P., Wongwiwatthananukit, S., Tanamatayarat, P., Toyama, O., Songsak, T, Pezzuto, J.M., Chang, L.C. (2012). Anti-inflammatory sesquiterpene lactones from the flower of Vernonia cinerea. Bioorg. Med. Chem. Lett. 22, 5559-62.

Yao, G.M., Sebisubi, F. M., Voo, L. K., Ho, C. C., Tan, G.T., Chang, L.C. (2011). Citrinin Derivatives from the Soil Filamentous Fungus Penicillium sp. H9318. J. Braz. Chem. Soc. 22, 1125-9.

Cheenpracha, S., Park, E-J., Yoshida, W.Y., Barit, C., Wall, M., Pezzuto, J.M., Chang, L.C. (2010). Potential Anti-inflammatory Phenolic Glycosides from the Medicinal Plant Moringa oleifera Fruits. Bioorg. Med. Chem.17, 6598-02.

Publication list via PubMed