Induction of apoptosis in human bladder cancer cells by triterpenoids isolated fromHolarrhena antidysentericathrough differential reactive oxygen species generation

A novel triterpenoid, holarol(1),3 beta-lup-20(31)-en-3,29,30-triol along with oneseco-triterpenoid, dihydrocanaric acid(2) and one known pentacyclic triterpenoid, betulin(3)have been isolated fromHolarrhena antidysenterica(L.)Wall. (Family: Apocynaceae).The structures of the compounds were elucidated by extensive IR, 1D, 2D NMR and mass spectrometric analysis. The optimised geometry of(1)was calculated by density-functional theory (DFT) using M06-2X hybrid functional and 6-31 G(D) basis set. The compounds showed differential cytotoxic activities in the cell lines-HeLa, EAC, Raji and T24.Seco-triterpenoid(2)showed highest sensitivity (IC50: 1.710 mu g/mL) against the bladder cancer cell line T24 followed by(1)(IC(50)9.698 mu g/mL) and(3)(IC(50)11.769 mu g/mL). Compound(1)showed highest reactive oxygen species (ROS) generation in T24 cell line followed by(3)and(2)resulting in induction of apoptosis through activation of caspase, cleavage of PARP and reduction of Bcl-2/Bax ratio. Thus compounds(1),(2)along with(3)could be potent anticancer agents.

Automated summary

A novel triterpenoid and two other triterpenoids, including holarol(1) and oneseco-triterpenoid(2), were isolated from Holarrhena antidysenterica(L.)Wall. These compounds demonstrated cytotoxic activities and potential as anticancer agents, with holarol(1) and oneseco-triterpenoid(2) showing high sensitivity against bladder cancer cell line T24.