Verrucarin A in cancer therapy
Pancreatic cancer (ductal pancreatic adenocarcinoma / PDA) is one of the most difficult cancers to treat. Common chemotherapeutic agents often only bring about a short-term improvement in symptoms and, unfortunately, experience has shown that they have little effect on the patient’s recovery. New types of therapy are urgently needed here.
This is where Verrucarin A comes into play. Trichothecenes are mycotoxins that inhibit protein synthesis and cause ribotoxic stress reactions in mammalian cells. Verrucarin A (VC-A) is a type D macrocyclic mycotoxin. It inhibits cell proliferation and causes apoptosis in breast cancer cells.
Verrucarin A and its potent anti-tumor activity
Verrucarin A also affects PDA cells. Strong anti-tumor activity is observed here. Verrucarin A strongly inhibits proliferation and blocks cells in the S phase. Blocking the progression of the cell cycle goes hand in hand with the inhibition of the cell cycle regulatory proteins cyclin D1, cyclin E, cyclin-dependent kinases (cdks) cdk2, cdk4 and cdk inhibitor WAF1 / 21.
Verrucarin A causes apoptosis in PDA cells, as shown by the increased annexin V-FITC binding, cleavage of poly (ADP-ribose) polymerase 1 (PARP-1) and procaspases-3, -8 and -9. VC-A also causes mitochondrial depolarization and release of cytochrome c and inhibits proteins of the Bcl-2 family that regulate apoptosis (Bcl-2, Bcl-xL, Bax and Bad).
Verrucarin A reduces apoptosis inhibitors
Verrucarin A also reduces the apoptosis inhibitors survivin and c-IAP-2. It downregulates the expression of prosurvival phospho-Akt (p-Akt), core factor κB (NF-κB) (p65) and mammalian target of rapamycin (p-mTOR) signaling proteins and their downstream mediators.
In conclusion, it can be said: The research results show a strong antiproliferative and apoptosis-inducing activity of verrucarin A for PDA cells due to the arrest of the cell cycle and inhibition of the prosurvival (anti-apoptotic) AKT / NF-κB / mTOR signal.
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