Unveiling the Mechanisms of Apoptosis Induction by Deep-Sea-Derived Polyketide-Terpenoid Hybrids from Penicillium allii-sativi: A Focus on Mitochondrial and mTOR Pathways
Chun-Lan Xie
Hainan Pharmaceutical Research and Development Science Park, Hainan Academy of Medical Sciences, Hainan Medical University, No. 3 Xueyuan Road, Haikou, Hainan, 571199 China
Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, 184 Daxue Road, Xiamen, Fujian, 361005 China
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen, Fujian, 361102 China
These authors contributed equally.
Search for more papers by this authorTai-Zong Wu
Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, 184 Daxue Road, Xiamen, Fujian, 361005 China
These authors contributed equally.
Search for more papers by this authorDuo Zhang
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen, Fujian, 361102 China
These authors contributed equally.
Search for more papers by this authorYuan Wang
Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, 184 Daxue Road, Xiamen, Fujian, 361005 China
Search for more papers by this authorTing Lin
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen, Fujian, 361102 China
Search for more papers by this authorHai-Feng Chen
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen, Fujian, 361102 China
Search for more papers by this authorXiao-Kun Zhang
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen, Fujian, 361102 China
Search for more papers by this authorCorresponding Author
Xian-Wen Yang
Hainan Pharmaceutical Research and Development Science Park, Hainan Academy of Medical Sciences, Hainan Medical University, No. 3 Xueyuan Road, Haikou, Hainan, 571199 China
Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, 184 Daxue Road, Xiamen, Fujian, 361005 China
E-mail: [email protected]Search for more papers by this authorChun-Lan Xie
Hainan Pharmaceutical Research and Development Science Park, Hainan Academy of Medical Sciences, Hainan Medical University, No. 3 Xueyuan Road, Haikou, Hainan, 571199 China
Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, 184 Daxue Road, Xiamen, Fujian, 361005 China
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen, Fujian, 361102 China
These authors contributed equally.
Search for more papers by this authorTai-Zong Wu
Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, 184 Daxue Road, Xiamen, Fujian, 361005 China
These authors contributed equally.
Search for more papers by this authorDuo Zhang
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen, Fujian, 361102 China
These authors contributed equally.
Search for more papers by this authorYuan Wang
Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, 184 Daxue Road, Xiamen, Fujian, 361005 China
Search for more papers by this authorTing Lin
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen, Fujian, 361102 China
Search for more papers by this authorHai-Feng Chen
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen, Fujian, 361102 China
Search for more papers by this authorXiao-Kun Zhang
School of Pharmaceutical Sciences, Xiamen University, South Xiangan Road, Xiamen, Fujian, 361102 China
Search for more papers by this authorCorresponding Author
Xian-Wen Yang
Hainan Pharmaceutical Research and Development Science Park, Hainan Academy of Medical Sciences, Hainan Medical University, No. 3 Xueyuan Road, Haikou, Hainan, 571199 China
Key Laboratory of Marine Genetic Resources, Third Institute of Oceanography, Ministry of Natural Resources, 184 Daxue Road, Xiamen, Fujian, 361005 China
E-mail: [email protected]Search for more papers by this authorComprehensive Summary
A chemical investigation of the deep-sea-derived fungus Penicillium allii-sativi MCCC 3A00580 resulted in the discovery of four new meroterpenoids (1—4) and one related known co-metabolite (5). These meroterpenoids showcase unique carbon skeletons featuring a common drimane sesquiterpene part with highly diverse polyketide units. Particularly, compound 1 incorporates a salicylic acid moiety while 2 possesses a rare peroxide bridge in the polyketide part. The structures of new compounds were assigned by extensive spectroscopic analysis, quantum calculations, and biogenetic considerations. Notably, 3 significantly blocked the mTOR signaling pathway, resulting in the arrest of cell cycle at G0-G1 phase and triggering mitochondrial apoptosis in Hela cells. While the previously reported co-metabolite macrophorin A (MPA) effectively triggered cell death in MDA-MB-231 cancer cells by activating apoptosis pathways involving death receptors, mitochondria, mTOR, and TNF.
Supporting Information
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