[CAS NO. 20874-52-6]  Saikosaponin D

Saikosaponin D is a novel autophagic inducer that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. Saikosaponin D increases cytosolic calciumlevel via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca2+ATPase pump, leading to autophagy induction through the activation of the Ca2+/calmodulin-dependent kinase kinase-AMP-activated protein kinase-mammalian target of rapamycin pathway. Its treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd can exhibit anti-cancer activities, which is mediated by the induction of apoptosis and autophagic cell death regardless of p53 status. Low dose Ssd is capable of sensitizing chremosensitive or chemoresistant lung and cervical cancer or hepatoma cells to anti-cancer drug- or radiation-induced apoptosis. Ssd also down-regulates PPM1D content, leading to the activation of Chk1, phosphorylation of Cdc25c and Cdk1, and subsequent G2/M arrest and apoptosis.