2. Academic Validation
  3. Eurochevalierines A - I, Sesquiterpene Alkaloid Hybrids with Anti-Triple Negative Breast Cancer Activity from Penicillium sp. HZ-5

Eurochevalierines A - I, Sesquiterpene Alkaloid Hybrids with Anti-Triple Negative Breast Cancer Activity from Penicillium sp. HZ-5

  • J Agric Food Chem. 2024 Jul 17. doi: 10.1021/acs.jafc.4c04011.
Yeting Zhang 1,  Qing Li 2 3,  Jinlong Zhang 1,  Ming Chen 1,  Xuan Li 1,  Yuben Qiao 4,  Kuansong Wang 2 3,  Changxing Qi 1 5,  Yonghui Zhang 1
Affiliations

Affiliations

  • 1 Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
  • 2 Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.
  • 3 Department of Pathology, School of Basic, Medical Science, Central South University, Changsha, Hunan 410013, China.
  • 4 State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan 430062, China.
  • 5 Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, China.
PMID: 39016690 DOI: 10.1021/acs.jafc.4c04011
Abstract

Nine new sesquiterpene Alkaloids, eurochevalierines A-I (1-9), were separated from the rice cultures of the endophytic fungus Penicillium sp. HZ-5 originated from the fresh leaf of Hypericum wilsonii N. Robson. The structures' illumination was conducted by single-crystal X-ray diffraction, extensive spectroscopic analysis, alkaline hydrolysis reaction, and Snatzke's method. Importantly, the antitumor activities screen of these isolates indicated that 1 could suppress triple negative breast Cancer (TNBC) cell proliferation and induce Apoptosis, with an IC50 value of 5.4 μM, which is comparable to the positive control docetaxel (DXT). Flow cytometry experiments mentioned that compound 1 significantly reduced mitochondrial membrane potential (MMP) of TNBC cells. In addition, 1 could activate Caspase-3 and elevated the levels of Reactive Oxygen Species (ROS) and expressions of suppressive cytokines and chemokines. Further Western blot analysis showed that 1 could selectively induce mitochondria-dependent Apoptosis in TNBC cells via the Bax/Bcl-2 pathway. Remarkably, these finding provide a new natural product skeleton for the treatment of TNBC.

Keywords

Penicillium sp; hybrids; sesquiterpene alkaloid; triple negative breast cancer.

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