Lupane Triterpene Derivatives Improve Antiproliferative Effect on Leukemia Cells through Apoptosis Induction.
Lía S Valencia-ChanNeptis Estrada-AlfaroJimmy Josué Ceballos-CruzLuis W Torres-TapiaSergio R Peraza-SánchezMoo-Puc Rosa EstherPublished in: Molecules (Basel, Switzerland) (2022)
Leukemia is one of the most frequent types of cancer. No effective treatment currently exists, driving a search for new compounds. Simple structural modifications were made to novel triterpenes isolated from Phoradendron wattii . Of the three resulting derivatives, 3α-methoxy-24-hydroxylup-20(29)-en-28-oic acid ( T1m ) caused a decrease in the median inhibitory concentration (IC 50 ) on the K562 cell line. Its mode of action was apparently apoptosis, ROS generation, and loss of mitochondrial membrane potential (MMP). Molecular docking analysis showed T1m to produce lower binding energies than its precursor for the Bcl-2 and EGFR proteins. Small, simple, and viable modifications to triterpenes can improve their activity against leukemia cell lines. T1m is a potentially promising element for future research. Clarifying the targets in its mode of action will improve its applicability.
Keyphrases
- cell cycle arrest
- molecular docking
- cell death
- oxidative stress
- acute myeloid leukemia
- induced apoptosis
- bone marrow
- endoplasmic reticulum stress
- pi k akt
- small cell lung cancer
- molecular dynamics simulations
- dna damage
- papillary thyroid
- epidermal growth factor receptor
- reactive oxygen species
- density functional theory
- signaling pathway
- climate change
- combination therapy