To develop drugs to kill cancer cells, we chemically synthesized a number of anti-cancer agents by adding different side chains to the core backbone of saponin. With the use of bioassay-guided methods, we found one agent that possessed a high cytotoxicity to a number of cancer cell lines. Interestingly, this compound was later found to be an active component of a tradition Chinese herb Paris polyphylla known as Polyphyllin D (PD) (diosgenyl α-L-rhamnopyranosyl- (1→2)-(β-L-ara-binofuranosyl-(1→4)-β-D-glucopyranoside). In China, the rhizome of Paris polyphylla (Chong Lou) has been used as a traditional Chinese medicine to treat a number of cancers including pancreas and liver cancers for a long time. Results from our laboratory demonstrate that PD is a potent anti-cancer agent that bypasses multi-drug resistance (MDR) and induces programmed cell death in R-HepG2 cells over-expressing P-glycoprotein (P-gp). In this paper, we reviewed the mechanisms how PD overcomes the MDR and exhibits a stronger cytotoxicity in the R-HepG2 than its parent line without P-gp through mitochondrial injury.
Keywords: Polyphyllin D, apoptosis, multi-drug resistance, mitochondria, R-HepG2
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