Leng Chee Chang, PhD
Associate Member, University of Hawaiʻi Cancer Center
Academic Appointment(s):
Professor, The Daniel K. Inouye College of Pharmacy, University of Hawaiʻi at Hilo
Affiliation: Tropical Conservation Biology and Environmental Science (TCBES), College of Natural and Health Sciences, University of Hawaiʻi at Hilo
Degree(s):
PhD, Natural Product Chemistry, Program of Collaborative Research in the Pharmaceutical Sciences, 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, marine algae, 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.
According to the United States Centers for Disease Control and Prevention and the University of Hawaiʻi Cancer Center, liver cancer occurs at higher rates in Hawaiʻi. Dr. Chang is interested in pursuing natural products as a potential chemotherapeutic target associated with liver cancer. Dr. Chang has worked on the Nuclear factor kappa B (NF-κB) inhibitors as cancer chemotherapeutic targets. NF-κB play roles in different cellular responses and regulate the expression of pro-inflammatory cytokines and cell cycle-regulatory components. Abnormal NF-κB upregulation may play vital roles of inflammation-induced carcinogenesis, including cholangiocarcinoma. It has been shown to play roles in growth, metastasis, and chemo-resistance of cancer. 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 is the discovery of natural products-derived NF-κB inhibitors and studying the mechanism of the aberrant NF-κB pathways associated with cancer (UH Cancer Center collaborator, publications and a US patent).
Currently, Dr. Chang's team is studying Waltheria indica (ʻuhaloa), Physalis peruviana (poha berry), Vernonia cinerea, Morinda citrifolia (noni), 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
Kaimuangpak K, Tamprasit K, Date A, Wongwiwatthananukit S, Chang LC, Weerapreeyakul N. (2023). Synthesis of bioactive spherical silver nanoparticles with surface plasmon resonance using ethanol twig of Cratoxylum formosum ssp. pruniflorum. Journal of Drug Delivery Science and Technology. 88, 104897.
Liu FF, O’Donnell TL, Park E-J, Kovacs S, Nakamura K, Dave A, Luo Y, Sun R, Wall M, Wongwiwatthananukit S, Silva DK, Williams PG, Pezzuto JP, Chang LC. (2023) Anti-inflammatory Quinoline Alkaloids from the Roots of Waltheria indica. J. Nat. Prod. Feb 6, 2023. DOI: 10.1021/acs.jnatprod.2c00861.
Sun A, Kondratyuk T, Wongwiwatthananukit S, Sun Dq, Chang LC. (2022) Investigation of Antioxidant, Anticancer, and Chemopreventive Properties of Hawaiian Grown Māmaki tea (Pipiturus albidus) Natural Product Communications. 17 (13):1-7.
Liu FF, Mallick S, O’Donnell TJ, Rouzimaimaiti R, Luo Y, Sun R, Wall M, Wongwiwatthananukit S, Date A, Silva DK, Williams PG, Chang LC. (2022) Coumarinolignans with reactive oxygen species and NF-κB inhibitory Activities from the Roots of Waltheria indica. Molecules. 27, 3270.
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, Sripisut T, Miklossy G, Turkson J, Laphookhieo S, Chang LC. (2017) Bioactive Polyprenylated Benzophenone derivatives from the fruits extracts of Garcinia xanthochymus. Bioorg. Med. Chem. Lett 27(16): 3760-3765.
Park EJ, Sang-ngern M, Chang LC, Pezzuto JM. (2016) Induction of cell cycle arrest and apoptosis with downregulation of Hsp90 client proteins and histone modification by 4β-hydroxywithanolide E isolated from Physalis peruviana. Mol. Nutr. Food Res. 60(6): 1482-500.
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
Patents
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).
Physalactone and 4-β-hydroxywithanolide E isolated from Physalis peruviana L. inhibit LPS-induced expression of COX-2 and INOS accompanied by abating Akt and STAT1. Chang LC, Pezzuto J, Sang-ngern M, and Park EJ. University of Hawaii of Technology Transfer (OTT) Invention Disclosure (19/0014). 10/12/2018.
Natural products that inhibits Nuclear Factor-kappa B activity. Chang LC, Silva DK, Wongwiwatthananukit S, Liu FF, and Mallick S. US provisional patent application number 63/092,364 10/15/2020.
Active Grants
L.C. Chang, PI (Non-Federal Entity/Federal Agency); Wall, Agency PI
USDA-ARS
58-2020-0-011
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.
08/31/2020-09/01/2025
L.C. Chang, PI; Co-Investigators: Dr. Vivek R. Nerurkar (Dept. Tropical Medicine, Medical Microbiology and Pharmacology, JABSOM UH Manoa), Dr. Supakit Wongwiwatthananukit (DKICP, UH Hilo)
Agency: Hawaii Community Foundation Medical Program
Evaluation of Natural Products Derived from Medicinal Plants and Marine algae with Antiviral Activity
The major aims of this project are to (1) evaluate antiviral activity of selected Medicinal plants and marine algae extracts against SARS-CoV-2; (2) Identify natural products with antiviral activity.
09/30/2023-12/01/2024
