Ganoderma tsugae Inhibits the SREBP-1/AR Axis Leading to Suppression of Cell Growth and Activation of Apoptosis in Prostate Cancer Cells.
Shih-Yin HuangGuan-Jhong HuangHsi-Chin WuMing-Ching KaoWen-Chin HuangPublished in: Molecules (Basel, Switzerland) (2018)
Recent research suggests that the activation of lipid biosynthesis (lipogenesis) is linked with prostate cancer (PCa) malignancy. Sterol regulatory element-binding protein-1 (SREBP-1) is a key transcriptional regulator controlling lipogenesis. Moreover, androgen receptor (AR) has been well defined to play an important role in lethal PCa aggressiveness from androgen-responsive to castration-resistant status. In this study, we showed that the quality-assured Ganoderma tsugae ethanol extract (GTEE), a Chinese natural and herbal product, significantly inhibited expression of SREBP-1 and its downstream genes associated with lipogenesis in PCa cells. Through inhibiting SREBP-1, GTEE reduced the levels of intracellular fatty acids and lipids in PCa cells. Importantly, GTEE also downregulated the expression of AR and prostate-specific antigen (PSA) in both androgen-responsive and castration-resistant PCa cells. By blocking the SREBP-1/AR axis, GTEE suppressed cell growth and progressive behaviors, as well as activating the caspase-dependent apoptotic pathway in PCa cells. These data provide a new molecular basis of GTEE for the development of a potential therapeutic approach to treat PCa malignancy.
Keyphrases
- induced apoptosis
- cell cycle arrest
- prostate cancer
- cell death
- endoplasmic reticulum stress
- signaling pathway
- binding protein
- fatty acid
- oxidative stress
- poor prognosis
- transcription factor
- pi k akt
- type diabetes
- multiple sclerosis
- gene expression
- cell proliferation
- radical prostatectomy
- anti inflammatory
- adipose tissue
- skeletal muscle
- machine learning
- reactive oxygen species
- drug delivery
- cell wall
- heat shock
- data analysis