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Amygdalin Exerts Antitumor Activity in Taxane-Resistant Prostate Cancer Cells
Igor Tsaur1, Anita Thomas1, Michelle Monecke2
1Department of Urology and Pediatric Urology, University Medicine Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
Abstract:
Despite recent advances in the treatment of metastatic prostate cancer (PCa), resistance development after taxane treatments is inevitable, necessitating effective options to combat drug resistance. Previous studies indicated antitumoral properties of the natural compound amygdalin. However, whether amygdalin acts on drug-resistant tumor cells remains questionable. An in vitro study was performed to investigate the influence of amygdalin (10 mg/mL) on the growth of a panel of therapy-naïve and docetaxel- or cabazitaxel-resistant PCa cell lines (PC3, DU145, and LNCaP cells). Tumor growth, proliferation, clonal growth, and cell cycle progression were investigated. The cell cycle regulating proteins (phospho)cdk1, (phospho)cdk2, cyclin A, cyclin B, p21, and p27 and the mammalian target of rapamycin (mTOR) pathway proteins (phospho)Akt, (phospho)Raptor, and (phospho)Rictor as well as integrin β1 and the cytoskeletal proteins vimentin, ezrin, talin, and cytokeratin 8/18 were assessed. Furthermore, chemotactic activity and adhesion to extracellular matrix components were analyzed. Amygdalin dose-dependently inhibited tumor growth and reduced tumor clones in all (parental and resistant) PCa cell lines, accompanied by a G0/G1 phase accumulation. Cell cycle regulating proteins were significantly altered by amygdalin. A moderate influence of amygdalin on tumor cell adhesion and chemotaxis was observed as well, paralleled by modifications of cytoskeletal proteins and the integrin β1 expression level. Amygdalin may, therefore, block tumor growth and disseminative characteristics of taxane-resistant PCa cells. Further studies are warranted to determine amygdalin's value as an antitumor drug.
Insights
Amygdalin, a natural compound, effectively inhibited growth and reduced tumor clones in both drug-sensitive and taxane-resistant prostate cancer (PCa) cells. This suggests amygdalin
Area of Science:
- Oncology
- Natural Products Chemistry
- Cancer Therapeutics
Background:
- Metastatic prostate cancer (PCa) treatment faces inevitable resistance to taxane therapies.
- The natural compound amygdalin exhibits potential antitumoral properties, but its efficacy against drug-resistant PCa is unclear.
- Developing novel therapeutic strategies to overcome taxane resistance in PCa is crucial.
Purpose of the Study:
- To investigate the in vitro effects of amygdalin on therapy-naïve and taxane-resistant prostate cancer cell lines.
- To assess amygdalin's impact on tumor growth, proliferation, clonal formation, and cell cycle progression.
- To analyze amygdalin's influence on key cell cycle regulators, mTOR pathway proteins, cytoskeletal components, and cell adhesion/chemotaxis.
Main Methods:
- In vitro study using PC3, DU145, and LNCaP prostate cancer cell lines (parental and resistant to docetaxel/cabazitaxel).
- Treatment with amygdalin (10 mg/mL) and assessment of tumor growth, proliferation, clonal formation, and cell cycle.
- Analysis of cell cycle proteins, mTOR pathway proteins, integrin β1, cytoskeletal proteins, adhesion, and chemotaxis.
Main Results:
- Amygdalin demonstrated dose-dependent inhibition of tumor growth and reduced tumor clones in all tested PCa cell lines.
- Amygdalin induced G0/G1 phase cell cycle arrest and significantly altered cell cycle regulating proteins.
- Amygdalin moderately affected tumor cell adhesion and chemotaxis, with associated changes in cytoskeletal proteins and integrin β1.
Conclusions:
- Amygdalin exhibits significant antitumor activity against both sensitive and taxane-resistant prostate cancer cells in vitro.
- Amygdalin may counteract the growth and dissemination characteristics of taxane-resistant PCa.
- Further research is warranted to evaluate amygdalin's therapeutic potential in treating resistant prostate cancer.
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