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Emerging Therapeutic Activity of Davallia formosana on Prostate Cancer Cells through Coordinated Blockade of
Po-Fan Hsieh1,2,3, Wen-Ping Jiang4, Shih-Yin Huang1
1Graduate Institute of Biomedical Sciences, School of Medicine, China Medical University, Taichung 404, Taiwan.
Background:
Prostate cancer (PCa) is the most prevalent malignancy diagnosed in men in Western countries. There is currently no effective therapy for advanced PCa aggressiveness, including castration-resistant progression. The aim of this study is to evaluate the potential efficacy and determine the molecular basis of Davallia formosana (DF) in PCa. Methods: LNCaP (androgen-sensitive) and C4-2 (androgen-insensitive/castration-resistant) PCa cells were utilized in this study. An MTT-based method, a wound healing assay, and the transwell method were performed to evaluate cell proliferation, migration, and invasion. Intracellular fatty acid levels and lipid droplet accumulation were analyzed to determine lipogenesis. Moreover, apoptotic assays and in vivo experiments were conducted.
Results:
DF ethanol extract (DFE) suppressed proliferation, migration, and invasion in PCa cells. DFE attenuated lipogenesis through inhibition of the expression of sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FASN). Moreover, DFE decreased androgen receptor (AR) and prostate-specific antigen (PSA) expression in PCa cells. We further showed the potent therapeutic activity of DFE by repressing the growth and leading to apoptosis of subcutaneous C4-2 tumors in a xenograft mouse model.
Conclusions:
These data provide a new molecular basis of DFE in PCa cells, and co-targeting SREBP-1/FASN/lipogenesis and the AR axis by DFE could be employed as a novel and promising strategy for the treatment of PCa.
Insights
Davallia formosana extract (DFE) effectively inhibits prostate cancer (PCa) cell growth, migration, and invasion. DFE targets lipogenesis and the androgen receptor (AR) pathway, offering a promising new strategy for PCa treatment.
Area of Science:
- Phytochemistry
- Oncology
- Molecular Biology
Background:
- Prostate cancer (PCa) is a leading malignancy in men, with limited treatments for advanced or castration-resistant forms.
- Current therapies for aggressive PCa, particularly castration-resistant progression, remain ineffective.
- Investigating natural compounds like Davallia formosana offers potential for novel therapeutic strategies.
Purpose of the Study:
- To evaluate the efficacy of Davallia formosana (DF) in prostate cancer (PCa) treatment.
- To elucidate the molecular mechanisms underlying DF's anti-cancer effects.
- To assess DF's impact on PCa cell proliferation, migration, invasion, and lipogenesis.
Main Methods:
- Utilized androgen-sensitive (LNCaP) and castration-resistant (C4-2) PCa cell lines.
- Assessed cell proliferation, migration, and invasion using MTT, wound healing, and Transwell assays.
- Analyzed intracellular fatty acid levels, lipid droplet accumulation, apoptosis, and gene expression (SREBP-1, FASN, AR, PSA) in vitro and in vivo xenograft models.
Main Results:
- DF ethanol extract (DFE) significantly suppressed PCa cell proliferation, migration, and invasion.
- DFE attenuated lipogenesis by inhibiting sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FASN) expression.
- DFE reduced androgen receptor (AR) and prostate-specific antigen (PSA) expression, and inhibited tumor growth and induced apoptosis in vivo.
Conclusions:
- DFE demonstrates potent anti-prostate cancer activity by targeting both lipogenesis and the AR signaling pathway.
- Co-targeting SREBP-1/FASN/lipogenesis and the AR axis represents a novel and promising therapeutic strategy for PCa.
- Davallia formosana holds potential as a natural therapeutic agent for prostate cancer treatment.
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