Apigenin enhances sorafenib anti-tumour efficacy in hepatocellular carcinoma
Background: The “one drug-one target” paradigm has various limitations affecting drug efficacy, such as resistance profiles and adverse effects. Combinational therapies help reduce unexpected off-target effects and accelerate therapeutic efficacy. Sorafenib- an FDA-approved drug for liver cancer, ha...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-05-01
|
| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523324000457 |
| _version_ | 1797267173341659136 |
|---|---|
| author | Deepti Singh Mohammad Afsar Khan Dhruv Mishra Aditya Goel Mairaj Ahmed Ansari Kafil Akhtar Hifzur R. Siddique |
| author_facet | Deepti Singh Mohammad Afsar Khan Dhruv Mishra Aditya Goel Mairaj Ahmed Ansari Kafil Akhtar Hifzur R. Siddique |
| author_sort | Deepti Singh |
| collection | DOAJ |
| description | Background: The “one drug-one target” paradigm has various limitations affecting drug efficacy, such as resistance profiles and adverse effects. Combinational therapies help reduce unexpected off-target effects and accelerate therapeutic efficacy. Sorafenib- an FDA-approved drug for liver cancer, has multiple limitations. Therefore, it is recommended to identify an agent that increases its effectiveness and reduces toxicity. In this regard, Apigenin, a plant flavone, would be an excellent option to explore. Methods: We used in silico, in vitro, and animal models to explore our hypothesis. For the in vitro study, HepG2 and Huh7 cells were exposed to Apigenin (12-96 μM) and Sorafenib (1-10 μM). For the in vivo study, Diethylnitrosamine (DEN) (25 mg/kg) induced tumor-bearing animals were given Apigenin (50 mg/kg) or Sorafenib (10 mg/kg) alone and combined. Apigenin's bioavailability was checked by UPLC. Tumor nodules were studied macroscopically and by Scanning Electron Microscopy (SEM). Biochemical analysis, histopathology, immunohistochemistry, and qRT-PCR were done. Results: The results revealed Apigenin's good bioavailability. In silico study showed binding affinity of both chemicals with p53, NANOG, ß-Catenin, c-MYC, and TLR4. We consistently observed a better therapeutic efficacy in combination than alone treatment. Combination treatment showed i) better cytotoxicity, apoptosis induction, and cell cycle arrest of tumor cells, ii) tumor growth reduction, iii) increased expression of p53 and decreased Cd10, Nanog, ß-Catenin, c-Myc, Afp, and Tlr4. Conclusions: In conclusion, Apigenin could enhance the therapeutic efficacy of Sorafenib against liver cancer and may be a promising therapeutic approach for treating HCC. However, further research is imperative to gain more in-depth mechanistic insights. |
| first_indexed | 2024-03-07T22:55:10Z |
| format | Article |
| id | doaj.art-439cf31a97c849f0a5e65667377343af |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-04-25T01:12:22Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-439cf31a97c849f0a5e65667377343af2024-03-10T05:12:05ZengElsevierTranslational Oncology1936-52332024-05-0143101920Apigenin enhances sorafenib anti-tumour efficacy in hepatocellular carcinomaDeepti Singh0Mohammad Afsar Khan1Dhruv Mishra2Aditya Goel3Mairaj Ahmed Ansari4Kafil Akhtar5Hifzur R. Siddique6Molecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, IndiaMolecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, IndiaDepartment of Zoology, DAV College (PG), Maa Shakumbhari University, Muzaffarnagar-251001, IndiaDepartment of Biotechnology, SCLS, Jamia Hamdard University, New Delhi 110062, IndiaDepartment of Biotechnology, SCLS, Jamia Hamdard University, New Delhi 110062, IndiaDepartment of Pathology, JN Medical College, Aligarh Muslim University, Aligarh 202002, IndiaMolecular Cancer Genetics & Translational Research Lab, Section of Genetics, Department of Zoology, Aligarh Muslim University, Aligarh 202002, India; Corresponding author.Background: The “one drug-one target” paradigm has various limitations affecting drug efficacy, such as resistance profiles and adverse effects. Combinational therapies help reduce unexpected off-target effects and accelerate therapeutic efficacy. Sorafenib- an FDA-approved drug for liver cancer, has multiple limitations. Therefore, it is recommended to identify an agent that increases its effectiveness and reduces toxicity. In this regard, Apigenin, a plant flavone, would be an excellent option to explore. Methods: We used in silico, in vitro, and animal models to explore our hypothesis. For the in vitro study, HepG2 and Huh7 cells were exposed to Apigenin (12-96 μM) and Sorafenib (1-10 μM). For the in vivo study, Diethylnitrosamine (DEN) (25 mg/kg) induced tumor-bearing animals were given Apigenin (50 mg/kg) or Sorafenib (10 mg/kg) alone and combined. Apigenin's bioavailability was checked by UPLC. Tumor nodules were studied macroscopically and by Scanning Electron Microscopy (SEM). Biochemical analysis, histopathology, immunohistochemistry, and qRT-PCR were done. Results: The results revealed Apigenin's good bioavailability. In silico study showed binding affinity of both chemicals with p53, NANOG, ß-Catenin, c-MYC, and TLR4. We consistently observed a better therapeutic efficacy in combination than alone treatment. Combination treatment showed i) better cytotoxicity, apoptosis induction, and cell cycle arrest of tumor cells, ii) tumor growth reduction, iii) increased expression of p53 and decreased Cd10, Nanog, ß-Catenin, c-Myc, Afp, and Tlr4. Conclusions: In conclusion, Apigenin could enhance the therapeutic efficacy of Sorafenib against liver cancer and may be a promising therapeutic approach for treating HCC. However, further research is imperative to gain more in-depth mechanistic insights.http://www.sciencedirect.com/science/article/pii/S1936523324000457ApigeninSorafenibChemosenstizationChemopreventionDiethylnitrosamine |
| spellingShingle | Deepti Singh Mohammad Afsar Khan Dhruv Mishra Aditya Goel Mairaj Ahmed Ansari Kafil Akhtar Hifzur R. Siddique Apigenin enhances sorafenib anti-tumour efficacy in hepatocellular carcinoma Translational Oncology Apigenin Sorafenib Chemosenstization Chemoprevention Diethylnitrosamine |
| title | Apigenin enhances sorafenib anti-tumour efficacy in hepatocellular carcinoma |
| title_full | Apigenin enhances sorafenib anti-tumour efficacy in hepatocellular carcinoma |
| title_fullStr | Apigenin enhances sorafenib anti-tumour efficacy in hepatocellular carcinoma |
| title_full_unstemmed | Apigenin enhances sorafenib anti-tumour efficacy in hepatocellular carcinoma |
| title_short | Apigenin enhances sorafenib anti-tumour efficacy in hepatocellular carcinoma |
| title_sort | apigenin enhances sorafenib anti tumour efficacy in hepatocellular carcinoma |
| topic | Apigenin Sorafenib Chemosenstization Chemoprevention Diethylnitrosamine |
| url | http://www.sciencedirect.com/science/article/pii/S1936523324000457 |
| work_keys_str_mv | AT deeptisingh apigeninenhancessorafenibantitumourefficacyinhepatocellularcarcinoma AT mohammadafsarkhan apigeninenhancessorafenibantitumourefficacyinhepatocellularcarcinoma AT dhruvmishra apigeninenhancessorafenibantitumourefficacyinhepatocellularcarcinoma AT adityagoel apigeninenhancessorafenibantitumourefficacyinhepatocellularcarcinoma AT mairajahmedansari apigeninenhancessorafenibantitumourefficacyinhepatocellularcarcinoma AT kafilakhtar apigeninenhancessorafenibantitumourefficacyinhepatocellularcarcinoma AT hifzurrsiddique apigeninenhancessorafenibantitumourefficacyinhepatocellularcarcinoma |