Preferential cytotoxicity of crude drugs used in Japanese Kampo medicines against human pancreatic cancer PANC-1 and PSN-1 cells

Aim: Pancreatic cancer is the most aggressive cancer of all and has an exceptionally high global mortality rate, ranking seventh as the most frequent cause of cancer death. In order to identify an anti-pancreatic cancer drug, we screened 24 crude drugs used in Kampo medicine for preferential cytotoxicity based on anti-austerity strategy. Methods: Preferential cytotoxicity was determined by comparing the cytotoxicities against PANC-1 and PSN-1 human pancreatic cancer cells in normal medium (DMEM) and nutrient-deprived medium. The extracts that showed potent activity were then examined for the mechanism of cell death on ethidium bromide/acridine orange (EB/AO) double staining. Results: Among the 24 extracts examined, extract of andrographis herba (aerial part of Andrographis paniculata) had the most potent preferential cytotoxicity against both cell lines, with concentration at which 50% of cells died preferentially in NDM (PC₅₀) of 9.72 µg/mL (PANC-1) and 9.41 µg/mL (PSN-1), and extracts of isodonis herba (aerial part of Plectranthus japonicas), phellodendri cortex (bark of Phellodendron amurense), licopodium (spore of Lycopodium clavatum), and panacis japonici rhizoma (radix of Panax japonicas) had mild activity. On EB/AO double-staining of cells treated by these extracts, isodonis herba, licopodium, and panacis japonici rhizoma induced apoptosis-like cell death under nutrient starvation, whereas phellodendri cortex and andrographis herba induced necrosis-like cell death. Conclusion: The crude drugs used in Japanese Kampo medicines, isodonis herba, phellodendri cortex, licopodium, andrographis herba, and panacis japonici rhizoma, could be used in the treatment of pancreatic cancer and/or as sources of anti-pancreatic cancer drugs.