Leng Chee Chang, PhD

Leng Chee Chang, PhD

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Associate Member, University of Hawaiʻi Cancer Center

Academic Appointment(s):
Professor, The Daniel K. Inouye College of Pharmacy, University of Hawaiʻi at Hilo

PhD, Natural Product Chemistry, College of Pharmacy, University of Illinois at Chicago, Chicago, IL
MS, Organic Chemistry, National University of Malaysia, Sabah, Malaysia

Research Focus

Throughout history, natural products have been a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. The research interests of Dr. Chang are on the isolation, characterization, and biological evaluation of natural products of higher plant origin and microbes. Her long-term goal is to identify leads and compounds derived from natural products that are active against cancer and/or inflammation. Her research project will be performed through collaborations between different disciplines at the UH Cancer Center to guide the identification of natural products as anticancer drug leads.

Dr. Chang has worked on the Signal Transducer and Activator of Transcription Factor (STAT)3 inhibitors as cancer chemotherapeutic targets in the past. It is widely accepted that chronic inflammation plays a key role in cancer. Nuclear factor kappa B (NF-κB), an inducible transcription factor, is responsible for different cellular responses like the regulation of expression of pro-inflammatory cytokines and cell cycle-regulatory components. Abnormal NF-κB upregulation may play vital roles of inflammation-induced carcinogenesis. The central role of NF-κB in those pathologies makes it a target for the treatment of inflammatory diseases such as cancer. Currently, her work focuses on targeting the aberrant NF-κB pathways (UH Cancer Center collaborator, publications and a US patent). Her team is also interested in Thioredoxin reductase (TrxRs) as a potential chemotherapeutic target for anticancer drug development. TrxR isoform 1 have been observed in various malignancies including lung and hepatocellular carcinomas than in normal tissues.

Currently, Dr. Chang's team is studying Vernonia cinerea, Physalis peruviana (poha berry), Waltheria indica (ʻuhaloa), Osteomeles anthyllidifolia (ʻūlei), and a few native Hawaiian healing plants with potential anticancer activity. Her team is also evaluating the potential of Hawaiian medicinal plants as anticancer leads. 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 these plants is underway. Waltheria indica is often used in Hawaiian traditional medicine to treat throat ailments, cough and respiratory infections. The extract and compounds exhibited significant inhibitory activity on TNF-α induced NF-κB activation at 20 µg/mL in Luc-HEK293 cells percentages inhibition in the range of 46.5-92.9%. In particular, a series of natural products (lignanoids and alkaloids) are isolated from Waltheria indica.

Dr. Chang has several papers published in this area, and a US Patent (PCT/US14/043523) and provisional disclosures with collaborators.

Selected Publications

Zhang M, Yang X, Wei YZ, Marisa Wall M, Songsak T, Wongwiwatthananukit S , Chang LC.(2019). Bioactive Sesquiterpene Lactones Isolated from the Whole Plants of Vernonia cinerea J Nat Prod. 82(8):2124-2131. PMID: 31411887

Park EJ, Sang-Ngern M, Chang LC, Pezzuto JM. (2019). Physalactone and 4β-Hydroxywithanolide E Isolated from Physalis peruviana Inhibit LPS-Induced Expression of COX-2 and iNOS Accompanied by Abatement of Akt and STAT1. J Nat Prod. 82(3):492-499. PMID: 30649869

Ahmed T, Raiz Z, Jafri L, Mahmood R, Haq IU, Chang LC, Mirza B. (2019). Inhibition of mouse embryonic stem cell proliferation and induction of differentiation by natural products isolated from Rhazya stricta Decne. Pak J Pharm Sci. 32(4(Supplementary)):1885-1891. PMID: 31680088

Youn UJ, Park EJ, Kondratyuk TP, Sang-Ngern M, Wall MM, Wei Y, Pezzuto JM, Chang LC. (2016) Anti-inflammatory and Quinone Reductase Inducing Compounds from Fermented Noni (Morinda citrifolia) Juice Exudates. J Nat Prod. 79(6):1508-13. PMID: 27196335

Miklossy G, Youn UJ, Yue P, Zhang M, Chen C-H, Hilliard T, Paladino, D, Li Y, Choi J, Sarkaria J, Kawakami J, Wongwiwatthananukit S, Chen Y, Sun Dq, Chang LC, Turkson J. (2015). Hirsutinolide series inhibit STAT3 activity alter GCN1, MAP1B, Hsp105, G6PD, vimentin, TrxR1, and importin α-2 expression, and induce antitumor effects against human glioma. J. Med. Chem. 58(19): 7734-48.

Publication list via PubMed


Novel Sesquiterpenoid Stat3 Inhibitors. Inventors: Chang LC, Turkson J, Wongwiwatthananukit S, Youn UJ and Sun Dq. United States Patent (PCT/US14/043523), December 24, 2014.

Novel Sesquiterpenoid Stat3 Inhibitors. Inventors: Chang, LC, Turkson J, Wongwiwatthananukit S, Youn UJ and Sun Dq. United States Patent (PCT/US14/896,846), December 5, 2015. Allowed by the United States Patent and Trademark Office (USPTO).

Active Grants

L.C. Chang, PI (Non-Federal Entity/Federal Agency); Wall, Agency PI
Investigating Natural Compounds from Tropical Plants with Medicinal Activity
The major goals of this project are to investigate tropical plants in Hawaii and the U.S. Pacific Basin with medicinal activity.