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Neochlorogenic acid anchors MCU-based calcium overload for cancer therapy.
- Source :
-
Food & function [Food Funct] 2021 Nov 15; Vol. 12 (22), pp. 11387-11398. Date of Electronic Publication: 2021 Nov 15. - Publication Year :
- 2021
-
Abstract
- Cancer is a major threat to human health worldwide, yet the clinical therapies remain unsatisfactory. In this study, we found that a Tetrastigma hemsleyanum leaves flavone (TLF) intervention could achieve tumor inhibition. Besides, neochlorogenic acid (NA), which had the highest absorbance peak in the HPLC profile of TLF, showed superior anti-proliferation ability over TLF, and could effectively trigger apoptosis, restrain migration, and facilitate cytoskeleton collapse, suggesting its key role in TLF's anticancer property. Molecular docking analysis suggested that NA was capable of binding with mitochondrial Ca <superscript>2+</superscript> uniporter (MCU), and further experiments confirmed that NA upregulated the MCU level to permit excess calcium ion influx, leading to mitochondrial calcium imbalance, dysfunction, structure alteration, and ROS elevation. Moreover, tumor-bearing mice were applied to further confirm the excellent tumor inhibition ability of NA under Ca <superscript>2+</superscript> -abundant conditions. Therefore, this study uncovered that NA could effectively trigger robust MCU-mediated calcium overload cancer therapy, which could be utilized in novel strategies for future cancer treatment.
- Subjects :
- Animals
Cell Survival drug effects
Chlorogenic Acid chemistry
Chlorogenic Acid metabolism
Flavones metabolism
Hep G2 Cells
Humans
Male
Mice
Mice, Inbred BALB C
Molecular Docking Simulation
Neoplasms, Experimental
Plant Leaves chemistry
Quinic Acid chemistry
Quinic Acid metabolism
Vitaceae chemistry
Antineoplastic Agents chemistry
Antineoplastic Agents metabolism
Antineoplastic Agents pharmacology
Calcium chemistry
Calcium metabolism
Calcium Channels chemistry
Calcium Channels metabolism
Chlorogenic Acid analogs & derivatives
Quinic Acid analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 2042-650X
- Volume :
- 12
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Food & function
- Publication Type :
- Academic Journal
- Accession number :
- 34672304
- Full Text :
- https://doi.org/10.1039/d1fo01393a