Betulin Acid Ester Derivatives Inhibit Cancer Cell Growth by Inducing Apoptosis through Caspase Cascade Activation: A Comprehensive In Vitro and In Silico Study.
Paweł PęcakMarta ŚwitalskaElwira ChrobakGrzegorz BoryczkaEwa BębenekPublished in: International journal of molecular sciences (2022)
Betulin, or naturally occurring triterpene, possesses promising antiproliferative activity. To further explore this potential, thirty-eight betulin acid ester derivatives modified at the C-28 position were tested for antitumor activities. Four human cancer cell lines, MV4-11 (leukemia), A549 (lung), PC-3 (prostate), MCF-7 (breast) as well as the normal BALB/3T3 (mouse fibroblasts) cell line were examined using MTT and SRB assays. A few derivatives exhibited strong antiproliferative activity with IC 50 values between 2 and 5 µM. Subsequent mechanistic studies revealed that some derivatives induced apoptosis by inducing caspase-3/7 activity. A strong structure-activity correlation of tested compounds has been proposed along with experimental and in silico pharmacokinetic properties.
Keyphrases
- induced apoptosis
- endoplasmic reticulum stress
- oxidative stress
- papillary thyroid
- cell death
- signaling pathway
- structure activity relationship
- prostate cancer
- molecular docking
- endothelial cells
- squamous cell
- acute myeloid leukemia
- squamous cell carcinoma
- high throughput
- childhood cancer
- lymph node metastasis
- cell proliferation
- risk assessment
- molecular dynamics simulations
- human health
- climate change
- benign prostatic hyperplasia