Conjugation of Triterpenic Acids of Ursane and Oleanane Types with Mitochondria-Targeting Cation F16 Synergistically Enhanced Their Cytotoxicity against Tumor Cells.
Mikhail V DubininDarya A NedopekinaAnna I IlzorkinaAlena A SemenovaVyacheslav A SharapovEldar V DavletshinNatalia V MikinaYuri P BelskyAnna Yu SpivakVladimir S AkatovNatalia V BelosludtsevaJiankang LiuKonstantin N BelosludtsevPublished in: Membranes (2023)
The present work shows the cytotoxic effects of novel conjugates of ursolic, oleanolic, maslinic, and corosolic acids with the penetrating cation F16 on cancer cells (lung adenocarcinoma A549 and H1299, breast cancer cell lines MCF-7 and BT474) and non-tumor human fibroblasts. It has been established that the conjugates have a significantly enhanced toxicity against tumor-derived cells compared to native acids and also demonstrate selectivity to some cancer cells. The toxic effect of the conjugates is shown to be due to ROS hyperproduction in cells, induced by the effect on mitochondria. The conjugates caused dysfunction of isolated rat liver mitochondria and, in particular, a decrease in the efficiency of oxidative phosphorylation, a decrease in the membrane potential, and also an overproduction of ROS by organelles. The paper discusses how the membranotropic- and mitochondria-targeted effects of the conjugates may be related to their toxic effects.
Keyphrases
- cell death
- cancer therapy
- cell cycle arrest
- reactive oxygen species
- induced apoptosis
- oxidative stress
- endoplasmic reticulum
- drug delivery
- dna damage
- endothelial cells
- ionic liquid
- endoplasmic reticulum stress
- signaling pathway
- breast cancer cells
- young adults
- risk assessment
- induced pluripotent stem cells
- pi k akt
- pluripotent stem cells
- structural basis