Alpinumisoflavone Exhibits the Therapeutic Effect on Prostate Cancer Cells by Repressing AR and Co-Targeting FASN- and HMGCR-Mediated Lipid and Cholesterol Biosynthesis
Prostate cancer (PCa) is the most common cancer in men, and this has been mainly noticed in Western and Asian countries. The aggregations of PCa and castration-resistant PCa (CRPC) progression are the crucial causes in the mortality of patients without the effective treatment. To seek new remedies f...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
|
| Series: | Life |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-1729/12/11/1769 |
| _version_ | 1797467557732548608 |
|---|---|
| author | Praveenkumar Basavaraj Phakkhathorn Ruangsai Po-Fan Hsieh Wen-Ping Jiang Da-Tian Bau Guan-Jhong Huang Wen-Chin Huang |
| author_facet | Praveenkumar Basavaraj Phakkhathorn Ruangsai Po-Fan Hsieh Wen-Ping Jiang Da-Tian Bau Guan-Jhong Huang Wen-Chin Huang |
| author_sort | Praveenkumar Basavaraj |
| collection | DOAJ |
| description | Prostate cancer (PCa) is the most common cancer in men, and this has been mainly noticed in Western and Asian countries. The aggregations of PCa and castration-resistant PCa (CRPC) progression are the crucial causes in the mortality of patients without the effective treatment. To seek new remedies for the lethal PCa diseases is currently an urgent need. In this study, we endeavored to investigate the therapeutic efficacy of alpinumisoflavone (AIF), a natural product, in PCa. LNCaP (androgen- sensitive) and C4-2 (CRPC) PCa cells were used. An MTT-based method, soft agar colony forming assay, biological progression approaches were applied to determine cell viability, migration, and invasion. A fatty acid quantification kit, a cholesterol detection kit and oil red O staining were conducted to analyze the intracellular levels of lipids and cholesterols. Apoptosis assays were also performed. AIF reduced cell viability, migration, and invasion in PCa cells. The expression of androgen receptor (AR), fatty acid synthase (FASN), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was substantially inhibited by AIF treatment in PCa cells. Furthermore, by inhibiting FASN and HMGCR expression, AIF decreased the amounts of intracellular fatty acids, cholesterols, and lipid droplets in PCa cells. Significantly, through coordinated targeting FASN- and HMGCR-regulated biosynthesis and the AR axis, AIF activated the caspase-associated apoptosis in PCa cells. These results collectively demonstrated for the first time the potential of AIF as a novel and attractive remedy and provided an alternative opportunity to cure PCa malignancy. |
| first_indexed | 2024-03-09T18:55:21Z |
| format | Article |
| id | doaj.art-05951963eda04ea99342f1cfcad6cc59 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T18:55:21Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-05951963eda04ea99342f1cfcad6cc592023-11-24T05:30:40ZengMDPI AGLife2075-17292022-11-011211176910.3390/life12111769Alpinumisoflavone Exhibits the Therapeutic Effect on Prostate Cancer Cells by Repressing AR and Co-Targeting FASN- and HMGCR-Mediated Lipid and Cholesterol BiosynthesisPraveenkumar Basavaraj0Phakkhathorn Ruangsai1Po-Fan Hsieh2Wen-Ping Jiang3Da-Tian Bau4Guan-Jhong Huang5Wen-Chin Huang6Graduate Institute of Biomedical Sciences, School of Medicine, China Medical University, Taichung 404, TaiwanInternational Master’s Program of Biomedical Sciences, School of Medicine, China Medical University, Taichung 404, TaiwanGraduate Institute of Biomedical Sciences, School of Medicine, China Medical University, Taichung 404, TaiwanDepartment of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan 717, TaiwanGraduate Institute of Biomedical Sciences, School of Medicine, China Medical University, Taichung 404, TaiwanSchool of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, College of Chinese Medicine, China Medical University, Taichung 404, TaiwanGraduate Institute of Biomedical Sciences, School of Medicine, China Medical University, Taichung 404, TaiwanProstate cancer (PCa) is the most common cancer in men, and this has been mainly noticed in Western and Asian countries. The aggregations of PCa and castration-resistant PCa (CRPC) progression are the crucial causes in the mortality of patients without the effective treatment. To seek new remedies for the lethal PCa diseases is currently an urgent need. In this study, we endeavored to investigate the therapeutic efficacy of alpinumisoflavone (AIF), a natural product, in PCa. LNCaP (androgen- sensitive) and C4-2 (CRPC) PCa cells were used. An MTT-based method, soft agar colony forming assay, biological progression approaches were applied to determine cell viability, migration, and invasion. A fatty acid quantification kit, a cholesterol detection kit and oil red O staining were conducted to analyze the intracellular levels of lipids and cholesterols. Apoptosis assays were also performed. AIF reduced cell viability, migration, and invasion in PCa cells. The expression of androgen receptor (AR), fatty acid synthase (FASN), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was substantially inhibited by AIF treatment in PCa cells. Furthermore, by inhibiting FASN and HMGCR expression, AIF decreased the amounts of intracellular fatty acids, cholesterols, and lipid droplets in PCa cells. Significantly, through coordinated targeting FASN- and HMGCR-regulated biosynthesis and the AR axis, AIF activated the caspase-associated apoptosis in PCa cells. These results collectively demonstrated for the first time the potential of AIF as a novel and attractive remedy and provided an alternative opportunity to cure PCa malignancy.https://www.mdpi.com/2075-1729/12/11/1769alpinumisoflavoneandrogen receptoranti-prostate cancer efficacyapoptosisfatty acid synthase3-hydroxy-3-methylglutaryl-CoA reductase |
| spellingShingle | Praveenkumar Basavaraj Phakkhathorn Ruangsai Po-Fan Hsieh Wen-Ping Jiang Da-Tian Bau Guan-Jhong Huang Wen-Chin Huang Alpinumisoflavone Exhibits the Therapeutic Effect on Prostate Cancer Cells by Repressing AR and Co-Targeting FASN- and HMGCR-Mediated Lipid and Cholesterol Biosynthesis Life alpinumisoflavone androgen receptor anti-prostate cancer efficacy apoptosis fatty acid synthase 3-hydroxy-3-methylglutaryl-CoA reductase |
| title | Alpinumisoflavone Exhibits the Therapeutic Effect on Prostate Cancer Cells by Repressing AR and Co-Targeting FASN- and HMGCR-Mediated Lipid and Cholesterol Biosynthesis |
| title_full | Alpinumisoflavone Exhibits the Therapeutic Effect on Prostate Cancer Cells by Repressing AR and Co-Targeting FASN- and HMGCR-Mediated Lipid and Cholesterol Biosynthesis |
| title_fullStr | Alpinumisoflavone Exhibits the Therapeutic Effect on Prostate Cancer Cells by Repressing AR and Co-Targeting FASN- and HMGCR-Mediated Lipid and Cholesterol Biosynthesis |
| title_full_unstemmed | Alpinumisoflavone Exhibits the Therapeutic Effect on Prostate Cancer Cells by Repressing AR and Co-Targeting FASN- and HMGCR-Mediated Lipid and Cholesterol Biosynthesis |
| title_short | Alpinumisoflavone Exhibits the Therapeutic Effect on Prostate Cancer Cells by Repressing AR and Co-Targeting FASN- and HMGCR-Mediated Lipid and Cholesterol Biosynthesis |
| title_sort | alpinumisoflavone exhibits the therapeutic effect on prostate cancer cells by repressing ar and co targeting fasn and hmgcr mediated lipid and cholesterol biosynthesis |
| topic | alpinumisoflavone androgen receptor anti-prostate cancer efficacy apoptosis fatty acid synthase 3-hydroxy-3-methylglutaryl-CoA reductase |
| url | https://www.mdpi.com/2075-1729/12/11/1769 |
| work_keys_str_mv | AT praveenkumarbasavaraj alpinumisoflavoneexhibitsthetherapeuticeffectonprostatecancercellsbyrepressingarandcotargetingfasnandhmgcrmediatedlipidandcholesterolbiosynthesis AT phakkhathornruangsai alpinumisoflavoneexhibitsthetherapeuticeffectonprostatecancercellsbyrepressingarandcotargetingfasnandhmgcrmediatedlipidandcholesterolbiosynthesis AT pofanhsieh alpinumisoflavoneexhibitsthetherapeuticeffectonprostatecancercellsbyrepressingarandcotargetingfasnandhmgcrmediatedlipidandcholesterolbiosynthesis AT wenpingjiang alpinumisoflavoneexhibitsthetherapeuticeffectonprostatecancercellsbyrepressingarandcotargetingfasnandhmgcrmediatedlipidandcholesterolbiosynthesis AT datianbau alpinumisoflavoneexhibitsthetherapeuticeffectonprostatecancercellsbyrepressingarandcotargetingfasnandhmgcrmediatedlipidandcholesterolbiosynthesis AT guanjhonghuang alpinumisoflavoneexhibitsthetherapeuticeffectonprostatecancercellsbyrepressingarandcotargetingfasnandhmgcrmediatedlipidandcholesterolbiosynthesis AT wenchinhuang alpinumisoflavoneexhibitsthetherapeuticeffectonprostatecancercellsbyrepressingarandcotargetingfasnandhmgcrmediatedlipidandcholesterolbiosynthesis |