New Properties and Mitochondrial Targets of Polyphenol Agrimoniin as a Natural Anticancer and Preventive Agent

Abstract

Agrimoniin is a polyphenol from the group of tannins with antioxidant and anticancer activities. It is assumed that the anticancer action of agrimoniin is associated with the activation of mitochondria-dependent apoptosis, but its mitochondrial targets have not been estimated. We examined the direct influence of agrimoniin on different mitochondrial functions, including the induction of the mitochondrial permeability transition pore (MPTP) as the primary mechanism of mitochondria-dependent apoptosis. Agrimoniin was isolated from Agrimonia pilosa Ledeb by multistep purification. The content of agrimoniin in the resulting substance reached 80%, as determined by NMR spectroscopy. The cytotoxic effect of purified agrimoniin was confirmed on the cultures of K562 and HeLa cancer cells by the MTT assay. When tested on isolated rat liver mitochondria, agrimoniin at a low concentration (10 µM) induced the low-amplitude swelling, which was inhibited by the MPTP inhibitors ADP and cyclosporine A, activated the opening of MPTP by calcium ions and stimulated the respiration supported by succinate oxidation. Also, agrimoniin reduced the electron acceptor DCPIP in a concentration-dependent manner and chelated iron ions. Owing to all these properties, agrimoniin can stimulate apoptosis or activate mitochondrial functions, which can be helpful in the prevention and elimination of stagnant pathological states.

Agrimol B inhibits colon carcinoma progression by blocking mitochondrial function through the PGC-1α/NRF1/TFAM signaling pathway

“…Previous studies have shown that agrimophol could stimulate mitochondria-dependent apoptosis in cancer cells. Thus, Agr extracted from agrimophol also suppresses cell proliferation by enriching cells in the G phase ( 10 , 12 ). In this study, Agr was found to increase ROS generation, block Bcl-2 expression, and increase Caspase-3 and Bax expression to promote cancer cell apoptosis.…”

“…Agrimonia pilosa Ledeb., a traditional Chinese herb, possesses anti-inflammatory, antioxidant, and antinociceptive effects ( 7 – 9 ). Agrimophol (agrimol A, B, and C), the main constituent of A. pilosa Ledeb., has been widely investigated for the treatment of osteosarcoma, pancreatic carcinoma, prostatic carcinoma, and lung carcinoma ( 10 – 12 ). The correlation between an abnormal increase in mitochondrial membrane potential and poor therapeutic outcomes in CRC has been reported ( 13 ).…”

Anticancer potential of acetone extracts from selected Potentilla species against human colorectal cancer cells

“…A recent study revealed that agrimoniin stimulates apoptosis via the mitochondria pathway, inducing activity of the mitochondrial permeability transition pore (MPTP), which leads to mitochondria swelling and a decrease in energy production. Moreover, the authors found that agrimoniin is cytotoxic against K562 and HeLa cell lines ( Fedotcheva et al, 2021 ). The in vivo effects of tannin-rich acetone extracts from selected Potentilla species may vary from obtained in vitro results.…”

Nano-Based Drug Delivery of Polyphenolic Compounds for Cancer Treatment: Progress, Opportunities, and Challenges

“…Alongside these treatments, the accumulation of intracellular reactive oxygen species (ROS) has also been shown to be associated with the induction of apoptosis [ 73 ]. Agrimoniin is a type of polyphenolic compound derived from Agrimonia pilosa ledeb , a perennial herb that has been widely used in traditional Chinese medicine [ 74 ]. A study has shown that agrimoniin can significantly increase intracellular ROS levels and lead to the dysfunction of mitochondria, which finally triggers apoptosis of pancreatic cancer cells [ 53 ].…”