Dentatin from Clausena excavata Induces Apoptosis in HepG2 Cells via Mitochondrial Mediated Signaling

Hepatocellular carcinoma (HCC) is a primary liver cancer with high global incidence and mortality rates.Current candidate drugs to treat HCC remain lacking and those in use possess undesirable side effects. In thisinvestigation, the antiproliferative effects of dentatin (DTN), a natural coumarin, were evaluated on HepG2 cellsand DTN’s probable preliminary molecular mechanisms in apoptosis induction were further investigated. DTNsignificantly (p<0.05) suppressed proliferation of HepG2 cells with an IC50 value of 12.0 μg/mL, without affectinghuman normal liver cells, WRL-68 (IC50> 50 μg/mL) causing G0/G1 cell cycle arrest via apoptosis induction.Caspase colorimetric assays showed markedly increased levels of caspase-3 and caspase-9 activities throughoutthe treatment period. Western blotting of treated HepG2 cells revealed inhibition of NF-κB that triggers themitochondrial-mediated apoptotic signaling pathway by up-regulating cytoplasmic cytochrome c and Bax, anddown-regulating Bcl-2 and Bcl-xL. The current findings suggest DTN has the potential to be developed furtheras an anticancer compound targeting human HCC.