Steroids from the Deep-Sea-Derived Fungus Penicillium granulatum MCCC 3A00475 Induced Apoptosis via Retinoid X Receptor ( RXR )-α Pathway

• Published in: Marine drugs 2019-03, Vol.17 (3), p.178
• Main Authors: Xie, Chun-Lan, Zhang, Duo, Xia, Jin-Mei, Hu, Chao-Chao, Lin, Ting, Lin, Yu-Kun, Wang, Guang-Hui, Tian, Wen-Jing, Li, Zeng-Peng, Zhang, Xiao-Kun, Yang, Xian-Wen, Chen, Hai-Feng
• Format: Article
• Language: English
• Subjects: ADP; anti-tumor; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Aquatic Organisms - chemistry; Binders; Cancer; Carbon; Cell culture; Cell cycle; Cell Line, Tumor; Cell lines; Cell Proliferation - drug effects; Crystallography; Crystallography, X-Ray; Cytotoxicity; Deep sea; Deep sea environments; Deep water; Drug Screening Assays, Antitumor; ergostanes; Ergosterol - analogs & derivatives; Ergosterol - chemistry; Ergosterol - isolation & purification; Ergosterol - pharmacology; FDA approval; Fermentation; Fungi; G1 phase; G1 Phase Cell Cycle Checkpoints - drug effects; Geologic Sediments - microbiology; Granulation; Humans; Inhibitory Concentration 50; Liquid culture; Magnetic Resonance Spectroscopy; marine-derived fungus; Metabolism; Molecular Structure; NMR; Nuclear magnetic resonance; nuclear receptor; Penicillium; Penicillium - chemistry; Penicillium granulatum; Poly(ADP-ribose) polymerase; Proliferation; Receptors; Retinoid X Receptor alpha - metabolism; Retinoid X receptors; Ribose; Signal Transduction - drug effects; Single crystals; Sodium; Spectrum analysis; Steroid hormones; Steroids; Transcription; Tumor cell lines; Two dimensional analysis; X-ray crystallography
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md17030178

Five new ergostanes, penicisteroids D-H ( - ), were isolated from the liquid culture of the deep-sea-derived fungus 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 were confirmed unambiguously by the single-crystal X-ray crystallography. Compounds and ⁻ showed moderate antiproliferative effects selectively against 12 different cancer cell lines with IC values of around 5 μM. Compounds and , potent binders with Kd values of 13.8 and 12.9 μM, respectively, could induce apoptosis by a Retinoid X Receptor ( )- -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.