Modulation of Apoptosis and ER Stress Markers in Hepatocellular Carcinoma Cells by Irinotecan, Hesperidin, and Piperine
Aim: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, and there is a pressing need to explore novel therapeutic strategies that enhance the efficacy of existing treatments. This study aims to investigate the effects of irinotecan (IRT), hesperidin (HSP), and piperi...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Galenos Yayinevi
2024-11-01
|
| Series: | Haseki Tıp Bülteni |
| Subjects: | |
| Online Access: | https://www.hasekidergisi.com/articles/modulation-of-apoptosis-and-er-stress-markers-in-hepatocellular-carcinoma-cells-by-irinotecan-hesperidin-and-piperine/doi/haseki.galenos.2025.9962 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832583711576555520 |
|---|---|
| author | Serkan Sen Kardelen Kocaman Kalkan Canan Yilmaz Sefa Celik |
| author_facet | Serkan Sen Kardelen Kocaman Kalkan Canan Yilmaz Sefa Celik |
| author_sort | Serkan Sen |
| collection | DOAJ |
| description | Aim: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, and there is a pressing need to explore novel therapeutic strategies that enhance the efficacy of existing treatments. This study aims to investigate the effects of irinotecan (IRT), hesperidin (HSP), and piperine (PIP) on HCC (HepG2), focusing on their modulation of apoptosis-related genes and endoplasmic reticulum (ER) stress markers.
Methods: This study is an in vitro experimental study. IC50 values for IRT, HSP, and PIP were determined using MTT cell viability assays. Researchers performed total RNA extraction and quantitative PCR to assess mRNA levels of Bad, Bax, and p53 (apoptosis-related genes) and ATF4, CHOP, and GRP78 (ER stress markers).
Results: Irinotecan significantly upregulated the expression of Bad, Bax, and p53 genes, as well as ER stress markers such as ATF4, CHOP, and GRP78. Hesperidin-enhanced apoptotic gene expression and exacerbated ER stress. Piperine attenuated IRT-induced apoptosis and suppressed ER stress markers.
Conclusion: Combining IRT with HSP enhanced apoptosis and ER stress in HepG2 cells, suggesting synergistic potential against HCC. Conversely, IRT combined with PIP reduced apoptotic response and ER stress markers, possibly compromising IRT's efficacy. These findings highlight complex interactions between chemotherapeutic agents and natural compounds, warranting further exploration in combination therapies. |
| format | Article |
| id | doaj-art-44cf7c15119249278fed18e335dd9421 |
| institution | Kabale University |
| issn | 1302-0072 2147-2688 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Galenos Yayinevi |
| record_format | Article |
| series | Haseki Tıp Bülteni |
| spelling | doaj-art-44cf7c15119249278fed18e335dd94212025-01-28T07:13:53ZengGalenos YayineviHaseki Tıp Bülteni1302-00722147-26882024-11-0162526527110.4274/haseki.galenos.2025.9962Modulation of Apoptosis and ER Stress Markers in Hepatocellular Carcinoma Cells by Irinotecan, Hesperidin, and PiperineSerkan Sen0https://orcid.org/0000-0002-2884-4753Kardelen Kocaman Kalkan1https://orcid.org/0000-0002-5749-5687Canan Yilmaz2https://orcid.org/0000-0002-6799-6522Sefa Celik3https://orcid.org/0000-0002-5187-378XAfyonkarahisar Health Sciences University, Ataturk Vocational School of Health Services, Deparment of Medical Laboratory Techniques, Afyonkarahisar, TurkeyGazi University Faculty of Medicine, Department of Medical Biochemistry, Ankara, TurkeyGazi University Faculty of Medicine, Department of Medical Biochemistry, Ankara, TurkeyAfyonkarahisar Health Sciences University Faculty of Medicine, Department of Medical Biochemistry, Afyonkarahisar, TurkeyAim: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, and there is a pressing need to explore novel therapeutic strategies that enhance the efficacy of existing treatments. This study aims to investigate the effects of irinotecan (IRT), hesperidin (HSP), and piperine (PIP) on HCC (HepG2), focusing on their modulation of apoptosis-related genes and endoplasmic reticulum (ER) stress markers. Methods: This study is an in vitro experimental study. IC50 values for IRT, HSP, and PIP were determined using MTT cell viability assays. Researchers performed total RNA extraction and quantitative PCR to assess mRNA levels of Bad, Bax, and p53 (apoptosis-related genes) and ATF4, CHOP, and GRP78 (ER stress markers). Results: Irinotecan significantly upregulated the expression of Bad, Bax, and p53 genes, as well as ER stress markers such as ATF4, CHOP, and GRP78. Hesperidin-enhanced apoptotic gene expression and exacerbated ER stress. Piperine attenuated IRT-induced apoptosis and suppressed ER stress markers. Conclusion: Combining IRT with HSP enhanced apoptosis and ER stress in HepG2 cells, suggesting synergistic potential against HCC. Conversely, IRT combined with PIP reduced apoptotic response and ER stress markers, possibly compromising IRT's efficacy. These findings highlight complex interactions between chemotherapeutic agents and natural compounds, warranting further exploration in combination therapies.https://www.hasekidergisi.com/articles/modulation-of-apoptosis-and-er-stress-markers-in-hepatocellular-carcinoma-cells-by-irinotecan-hesperidin-and-piperine/doi/haseki.galenos.2025.9962irinotecanhesperidinpiperinecarcinomahepatocellularapoptosisendoplasmic reticulum |
| spellingShingle | Serkan Sen Kardelen Kocaman Kalkan Canan Yilmaz Sefa Celik Modulation of Apoptosis and ER Stress Markers in Hepatocellular Carcinoma Cells by Irinotecan, Hesperidin, and Piperine Haseki Tıp Bülteni irinotecan hesperidin piperine carcinoma hepatocellular apoptosis endoplasmic reticulum |
| title | Modulation of Apoptosis and ER Stress Markers in Hepatocellular Carcinoma Cells by Irinotecan, Hesperidin, and Piperine |
| title_full | Modulation of Apoptosis and ER Stress Markers in Hepatocellular Carcinoma Cells by Irinotecan, Hesperidin, and Piperine |
| title_fullStr | Modulation of Apoptosis and ER Stress Markers in Hepatocellular Carcinoma Cells by Irinotecan, Hesperidin, and Piperine |
| title_full_unstemmed | Modulation of Apoptosis and ER Stress Markers in Hepatocellular Carcinoma Cells by Irinotecan, Hesperidin, and Piperine |
| title_short | Modulation of Apoptosis and ER Stress Markers in Hepatocellular Carcinoma Cells by Irinotecan, Hesperidin, and Piperine |
| title_sort | modulation of apoptosis and er stress markers in hepatocellular carcinoma cells by irinotecan hesperidin and piperine |
| topic | irinotecan hesperidin piperine carcinoma hepatocellular apoptosis endoplasmic reticulum |
| url | https://www.hasekidergisi.com/articles/modulation-of-apoptosis-and-er-stress-markers-in-hepatocellular-carcinoma-cells-by-irinotecan-hesperidin-and-piperine/doi/haseki.galenos.2025.9962 |
| work_keys_str_mv | AT serkansen modulationofapoptosisanderstressmarkersinhepatocellularcarcinomacellsbyirinotecanhesperidinandpiperine AT kardelenkocamankalkan modulationofapoptosisanderstressmarkersinhepatocellularcarcinomacellsbyirinotecanhesperidinandpiperine AT cananyilmaz modulationofapoptosisanderstressmarkersinhepatocellularcarcinomacellsbyirinotecanhesperidinandpiperine AT sefacelik modulationofapoptosisanderstressmarkersinhepatocellularcarcinomacellsbyirinotecanhesperidinandpiperine |