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The antiandrogenic effect of neferine, liensinine, and isoliensinine by inhibiting 5-α-reductase and androgen receptor expression via PI3K/AKT signaling pathway in prostate cancer.
- Source :
-
Die Pharmazie [Pharmazie] 2021 May 01; Vol. 76 (5), pp. 225-231. - Publication Year :
- 2021
-
Abstract
- Neferine, liensinine, and isoliensinine are bisbenzylisoquinoline alkaloids extracted from seed-embryos of Nelumbo nucifera Gaertn. In this study, we evaluated the anticancer activities and mechanism of action of these natural products in prostate cancer cells by MTT, wound healing, ELISA and Western blotting. Neferine, liensinine, and isoliensinine showed growth inhibition and displayed a significant anti-migration activity in prostate cancer cells. They induced apoptosis and autophagy by activating cleaved caspase-9, cleaved PAPR, Bax, LC3B-II, but decreased Bcl-2 and PARP protein expression in LNCaP cells 24 h after treatments. The apoptotic and cytotoxic effects of neferine, liensinine, and isoliensinine were significantly attenuated in the presence of the caspase inhibitor, Z-VAD-FMK. However, the effects were enhanced in the presence of Akt inhibitor (MK2206) and PI3K inhibitor (LY294002). Moreover, neferine, liensinine, and isoliensinine also downregulated the protein expression of androgen receptor, prostate-specific antigen, and type II 5-α-reductase. These results demonstrated that these bisbenzylisoquinoline alkaloids have the potential as promising therapeutics agents. They induced apoptosis via inactivation with the PI3K/AKT signal pathway.
- Subjects :
- Amino Acid Chloromethyl Ketones pharmacology
Androgen Antagonists pharmacology
Antineoplastic Agents pharmacology
Apoptosis drug effects
Apoptosis Regulatory Proteins drug effects
Autophagy drug effects
Benzylisoquinolines chemistry
Biological Products therapeutic use
Cell Line, Tumor
Cell Movement drug effects
Chromones pharmacology
Heterocyclic Compounds, 3-Ring pharmacology
Humans
Isoquinolines chemistry
Male
Morpholines pharmacology
Nelumbo chemistry
Phenols chemistry
Phosphatidylinositol 3-Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
Signal Transduction
5-alpha Reductase Inhibitors pharmacology
Androgen Receptor Antagonists pharmacology
Benzylisoquinolines pharmacology
Isoquinolines pharmacology
Phenols pharmacology
Prostatic Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0031-7144
- Volume :
- 76
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Die Pharmazie
- Publication Type :
- Academic Journal
- Accession number :
- 33964997
- Full Text :
- https://doi.org/10.1691/ph.2021.1301