Chemical constituents of Callistemon citrinus from Egypt and their antiausterity activity against PANC-1 human pancreatic cancer cell line
| Autor: | Jun-ya Ueda, Ashraf M. Omar, Ahmed M Tawila, Naoki Toyooka, Sijia Sun, Dya Fita Dibwe, Min Jo Kim, Suresh Awale |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Programmed cell death
Myrtaceae Clinical Biochemistry Pharmaceutical Science Cell morphology 01 natural sciences Biochemistry Callistemon citrinus chemistry.chemical_compound Structure-Activity Relationship Pancreatic cancer Cell Line Tumor Drug Discovery medicine Tumor Microenvironment Humans Cytotoxicity Molecular Biology Arctigenin Cell Proliferation biology Cell Death Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Terpenes Organic Chemistry Cell migration biology.organism_classification medicine.disease Antineoplastic Agents Phytogenic 0104 chemical sciences Pancreatic Neoplasms 010404 medicinal & biomolecular chemistry chemistry Cancer cell Molecular Medicine Egypt Drug Screening Assays Antitumor |
| Zdroj: | Bioorganicmedicinal chemistry letters. 30(16) |
| ISSN: | 1464-3405 |
| Popis: | Human pancreatic cancer is resistant to almost all conventional chemotherapeutic agents. It is known to proliferate aggressively within hypovascular tumor microenvironment by exhibiting remarkable tolerance to nutrition starvation, a phenomenon termed as “austerity”. Search for the new agents that eliminate the tolerance of cancer cells to nutrition starvation is a promising strategy in anticancer drug discovery. In this study, two new meroterpenoids named callistrilones O and P (1 and 2) together with eight known triterpenes (3–10) were isolated from the active dichloromethane extract of Callistemon citrinus leaves. The structure elucidation of the new compounds was achieved by HRFABMS, 1D, 2D NMR, and ECD quantum calculations. All isolated compounds were tested for their preferential cytotoxicity against PANC-1 human pancreatic cancer cells. Among these, callistrilone O (1) exhibited the most potent preferential cytotoxicity with a PC50 value of 0.3 nM, the strongest activity with over 2000 times potent than the positive control arctigenin. Callistrilone O (1) induced dramatic alterations in PANC-1 cell morphology leading to cell death under nutrient-deprived conditions. Compound 1 also inhibited PANC-1 cell migration and -PANC-1 colony formation under the nutrient-rich condition. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect