Cytotoxicity of apigenin toward multiple myeloma cell lines and suppression of iNOS and COX-2 expression in STAT1-transfected HEK293 cells
| Autor: | Nuha Mahmoud, Thomas Efferth, Alaadin M. Naqishbandi, Sara Abdelfatah, Aveen Nozad Adham |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Programmed cell death
Pharmaceutical Science Nitric Oxide Synthase Type II Apoptosis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Drug Discovery Antineoplastic Combined Chemotherapy Protocols Autophagy Cytotoxic T cell Humans DAPI Apigenin 030304 developmental biology Cell Proliferation Pharmacology 0303 health sciences Dose-Response Relationship Drug Chemistry Cell Cycle Computational Biology Cell cycle Antineoplastic Agents Phytogenic HEK293 Cells STAT1 Transcription Factor Complementary and alternative medicine Cell culture Cyclooxygenase 2 Doxorubicin 030220 oncology & carcinogenesis Cancer cell Cancer research Molecular Medicine Multiple Myeloma Reactive Oxygen Species |
| Zdroj: | Phytomedicine : international journal of phytotherapy and phytopharmacology. 80 |
| ISSN: | 1618-095X |
| Popis: | Apigenin is one of the most abundant dietary flavonoids that possesses multiple bio-functions.This study was designed to determine the influence of apigenin on gene expressions, cancer cells, as well as STAT1/COX-2/iNOS pathway mediated inflammation and tumorigenesis in HEK293-STAT1 cells. Furthermore, the cytotoxic activity toward multiple myeloma (MM) cell lines was investigated.Bioinformatic analyses were used to predict the sensitivity and resistance of tumor cells toward apigenin and to determine cellular pathways influenced by this compound. The cytotoxic and ferroptotic activity of apigenin was examined by the resazurin reduction assay. Additionally, we evaluated apoptosis, and cell cycle distribution, induction of reactive oxygen species (ROS) and loss of integrity of mitochondrial membrane (MMP) by using the flow cytometry analysis. DAPI staining was used to detect characteristic apoptotic features. Furthermore, we verified its anti-inflammatory and additional mechanism of cell death by western blotting.COMPARE and hierarchical cluster analyses exhibited that 29 of 55 tumor cell lines were sensitive against apigenin (p0.001). The Ingenuity Pathway Analysis data showed that important bio-functions affected by apigenin were: gene expression, cancer, hematological system development and function, inflammatory response, and cell cycle. The STAT1 transcription factor was chosen as target protein on the basis of gene promoter binding motif analyses. Apigenin blocked cell proliferation of wild-type HEK293 and STAT1 reporter cells (HEK293-STAT1), promoted STAT1 suppression and subsequent COX-2 and iNOS inhibition. Apigenin also exhibited synergistic activity in combination with doxorubicin toward HEK293-STAT1 cells. Apigenin exerted excellent growth-inhibitory activity against MM cells in a concentration-dependent manner with the greatest activity toward NCI-H929 (ICApigenin may be a suitable candidate for MM treatment. The inhibition of the STAT1/COX-2/iNOS signaling pathway by apigenin is an important mechanism not only in the suppression of inflammation but also in induction of apoptosis. |
| Databáze: | OpenAIRE |
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