Evaluating the Therapeutic Effect of Hispidin on Prostate Cancer Cells.

Androgen deprivation therapy (ADT) is the primary treatment for advanced prostate cancer (PCa). However, prolonged ADT inevitably results in therapy resistance with the emergence of the castration-resistant PCa phenotype (CRPC). Hence, there is an urgent need to explore new treatment options capable of delaying PCa progression. Hispidin (HPD) is a natural polyketide primarily derived from plants and fungi. HPD has been shown to have a diverse pharmacological profile, exhibiting anti-inflammatory, antiviral, cardiovascular and neuro-protective activities. However, there is currently no research regarding its properties in the context of PCa treatment. This research article seeks to evaluate the anti-cancer effect of HPD and determine the underlying molecular basis in both androgen-sensitive PCa and CRPC cells. Cell growth, migration, and invasion assays were performed via the MTS method, a wound healing assay and the transwell method. To investigate if HPD affected the expression of proteins, Western blot analysis was conducted. Furthermore, apoptosis was assessed by Annexin V-FITC/PI staining and Western blot analyses. HPD exhibited a favorable pharmaceutical profile to inhibit cell growth; disrupt the cell cycle; attenuate wound healing, migration and invasion; and induce apoptosis in PCa cells in vitro. The mechanistic results demonstrated that HPD reduced AR, MMP-2 and MMP-9 expression and activated the caspase-related pathway, leading to programmed cell death in PCa cells. We showed the anti-cancer effect of HPD on PCa cells and confirmed its feasibility as a novel therapeutic agent. This study provides significant insights into the delineation of the molecular mechanism of HPD in PCa cells and the development of an effective and safe therapy using HPD to eliminate PCa progression.

Elucidation of scandenolone as anti-cancer activity through impairment of the metabolic and signaling vulnerabilities in prostate cancer.

Prostate cancer (PCa) is the most prevalent men's cancer in America and Western countries. No effective therapies are currently available for PCa aggressiveness, including castration-resistant progression (CRPC). This study aims at evaluation of the prospective efficacy and the molecular mechanism of scandenolone (SCA), a natural isoflavone, in PCa progression. SCA suppressed cell viability and progression and induced apoptosis in PCa cells. SCA inhibited the expression of lipogenesis and cholesterogenesis related key genes. Through inhibition of these metabolic genes, SCA decreased the levels of fatty acids, lipid droplets and cholesterols in PCa cells. Moreover, SCA enhanced the expression of antioxidant factors, including Nrf2, HO-1, catalase and SOD-1, and reduced the ROS levels in PCa cells. Substantially, SCA displayed the potential efficacy on CRPC tumors. This paper offers a new insight into the underlying molecular basis of SCA in PCa cells. By coordinated impairment of the metabolic and signaling vulnerabilities, including lipogenesis, cholesterogenesis, ROS and the AR/PSA axis, SCA could be applied as a novel and promising remedy to cure malignant PCa.

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 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.

Cell suspension culture extract of Eriobotrya japonica attenuates growth and induces apoptosis in prostate cancer cells via targeting SREBP-1/FASN-driven metabolism and AR.

BACKGROUND: Castration-resistant prostate cancer (CRPC) is one of the main causes of male cancer mortality. There is currently no effective treatment to cure this deadly prostate cancer (PCa) progression. However, recent research showed that activation of lipogenesis leads to CRPC progression. It provides a rationale to target the highly lipogenic activity as a novel and promising therapy against lethal CRPC. PURPOSES: The present study aims to evaluate the anticancer efficacy and the molecular mechanism of cell suspension culture extract from Eriobotrya japonica (EJCE) in PCa, including CRPC. METHODS: Cell growth, migration and invasion analyses were performed by MTT method, a wound healing assay and the transwell method, respectively. Apoptosis was assessed by a flow cytometry-based Annexin V-FITC/PI assay, caspase enzymatic activity and Western blot analyses. Lipogenesis was determined by a Fatty Acid Quantification Kit and an Oil Red O staining. The in vivo experiment was conducted by a xenograft mouse model. RESULTS: PCa cell growth, migration and invasion were significantly affected by EJCE. EJCE decreased expression of sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FASN) in PCa cells, two main factors for lipogenesis. By inhibiting SREBP-1/FASN, EJCE reduced the intracellular fatty acid levels and lipid droplet accumulation in PCa. Moreover, EJCE down-regulated the androgen receptor (AR) and prostate-specific antigen (PSA) in PCa cells. Significantly, EJCE exhibited the potential anticancer activity by suppressing the growth and leading to apoptosis of CRPC tumors in a xenograft mouse model. CONCLUSION: These results reveal a novel therapeutic molecular mechanism of EJCE in PCa. Blockade of SREBP-1/FASN-driven metabolism and AR by EJCE could be employed as a potent opportunity to cure malignant PCa.

Emerging Therapeutic Activity of Davallia formosana on Prostate Cancer Cells through Coordinated Blockade of Lipogenesis and Androgen Receptor Expression.

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.