Steroids from the Deep-Sea-Derived Fungus Penicillium granulatum MCCC 3A00475 Induced Apoptosis via Retinoid X Receptor (RXR)-α Pathway.
Chun-Lan XieDuo ZhangJin-Mei XiaChao-Chao HuTing LinYu-Kun LinGuang-Hui WangWen-Jing TianZeng-Peng LiXiao-Kun ZhangXian-Wen YangHai-Feng ChenPublished in: Marine drugs (2019)
Five new ergostanes, penicisteroids D-H (1-5), were isolated from the liquid culture of the deep-sea-derived fungus Penicillium granulatum MCCC 3A00475, along with 27 known compounds. The structures of the new steroids were established mainly on the basis of extensive analysis of 1D and 2D NMR as well as HRESIMS data. Moreover, the absolute configurations of 1 were confirmed unambiguously by the single-crystal X-ray crystallography. Compounds 2 and 4⁻7 showed moderate antiproliferative effects selectively against 12 different cancer cell lines with IC50 values of around 5 μM. Compounds 2 and 6, potent RXRα binders with Kd values of 13.8 and 12.9 μM, respectively, could induce apoptosis by a Retinoid X Receptor (RXR)-α-dependent mechanism by regulating RXRα transcriptional expression and promoting the poly-ADP-ribose polymerase (PARP) cleavage. Moreover, they could inhibit proliferation by cell cycle arrest at the G0/G1 phase.
Keyphrases
- cell cycle arrest
- induced apoptosis
- endoplasmic reticulum stress
- signaling pathway
- pi k akt
- cell death
- high resolution
- oxidative stress
- poor prognosis
- binding protein
- magnetic resonance
- dna damage
- gene expression
- transcription factor
- high intensity
- big data
- squamous cell carcinoma
- dna repair
- magnetic resonance imaging
- cell proliferation
- deep learning
- young adults
- data analysis
- dual energy
- heat stress