Complementary effects of Orthosiphon stamineus standardized ethanolic extract and rosmarinic acid in combination with gemcitabine on pancreatic cancer
| Autor: | Chern E. Oon, Amin Malik Shah Abdul Majid, Ashwaq Hamid Salem Yehya, Muhammad Asif |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Notch signaling pathway Apoptosis Deoxycytidine Depsides 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Pancreatic cancer medicine Humans Orthosiphon Notch 1 biology Plant Extracts Rosmarinic acid Cancer Orthosiphon stamineus General Medicine Cell cycle medicine.disease biology.organism_classification Gemcitabine Pancreatic Neoplasms 030104 developmental biology chemistry Cinnamates 030220 oncology & carcinogenesis Cancer research medicine.drug |
| Zdroj: | Biomedical Journal. 44:694-708 |
| ISSN: | 2319-4170 |
| DOI: | 10.1016/j.bj.2020.05.015 |
| Popis: | Background Pancreatic cancer is one of the most notorious cancers and is known for its highly invasive characteristics, drug resistance, and metastatic progression. Unfortunately, resistance towards gemcitabine develops in many with advanced pancreatic cancer. Orthosiphon stamineus (O.s) is used widely as a traditional medicine for the treatment of multiple ailments, including cancer in South East Asia. The present in vitro study was designed to investigate complementary effects of an ethanolic extract of O.s (Et. O.s) compared to rosmarinic acid in combination with gemcitabine on Panc-1 (pancreatic cancer) cells. Method Cell viability and colony formation assays were used to determine the IC50 of Et. O.s, rosmarinic acid, and gemcitabine. Different doses of gemcitabine in combination with Et. O.s or rosmarinic acid were tested against Panc-1 to select the best concentrations which possessed synergistic effects. Elucidation of molecular mechanisms responsible for mediating chemo-sensitivity in Panc-1 was performed using qPCR, flow cytometry and staining techniques. Results Et. O.s was found to significantly sensitise Panc-1 towards gemcitabine by reducing expression of multidrug-resistant (MDR-1, MRP-4, and MRP-5) and epithelial-mesenchymal transition (ZEB-1 and Snail-1) genes through human equilibrate nucleoside transporter-1 (hENT-1) induction. Et. O.s-gemcitabine combination induced cellular senescence and cell death through cell cycle regulation and Notch pathway inhibition. In contrast, rosmarinic acid-gemcitabine combination showed no additional effects on cellular senescence, apoptosis, EMT markers, the MRP-4 and MRP-5 multi-drug resistance protein family, hENT-1, and the Notch pathway through Notch 1 intracellular domain. Conclusion This study provides valuable information on the use of Et. O.s to complement gemcitabine in targeting pancreatic cancer in vitro and demonstrates its potential use as a novel complementary treatment in pancreatic cancer patients. |
| Databáze: | OpenAIRE |
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