Tubeimoside-1 exerts cytotoxicity in HeLa cells through mitochondrial dysfunction and endoplasmic reticulum stress pathways.

Traditional Chinese herbal medicines are a great source of cancer chemotherapeutic agents. Tubeimoside-1 (TBMS1) is a triterpenoid saponin extracted from Bolbostemma paniculatum (Maxim.) Franquet (Cucurbitaceae), a Chinese herb with anticancer potential named as "Tu Bei Mu". In the present study, we used proteomics to examine the cytotoxic effects of TBMS1 on HeLa cells. Protein profiling of TBMS1-treated HeLa cells revealed profound protein alterations related to energy metabolism and protein synthesis and folding, suggesting that mitochondria and endoplasmic reticulum (ER) play a role in TBMS1-initiated apoptosis. TBMS1 induced the depletion of mitochondrial transmembrane potential (DeltaPsi(m)), leading to the activation of caspase-dependent apoptotic cell death. Unfolded Protein Response (UPR) signaling pathways are also activated after TBMS1 treatment and these changes were accompanied by increased expression of GADD153/CHOP, a transcription factor associated with growth arrest and apoptosis in the event of prolonged ER stress. Salubrinal (Sal), a selective inhibitor for ER stress, partially abrogated the TBMS1-related cell death. These results suggest that TBMS1 exerts cytotoxicity in HeLa cells through both mitochondrial dysfunction and ER stress cell death pathways.