Cytotoxic effects of triterpenoid saponins from Androsace umbellata against multidrug resistance (MDR) and non-MDR cells.
Cytotoxicity-guided fractionation and separation of MeOH extract from Androsace umbellata (Lour.) Merr. led to the isolation of four triterpenoid saponins. Compounds isolated from the n-BuOH soluble fraction were identified as saxifragifolin C (1), A (2), B (3), and D (4) by spectroscopic analysis. Antiproliferative effect of isolated compounds were evaluated by the sulforhodamin B assay against multidrug resistance (MDR; MES-SA/DX5 and HCT15/CLO2) and non-MDR (A549, SK-OV-3, SK-MEL-2, MES-SA, and HCT15) human tumor cell lines. All compounds exhibited strong cytotoxicity against non-MDR human tumor cell lines with IC(50) values of 0.19-2.37 muM. MDR cells and non-MDR cells had similar sensitivity to these compounds, however, MDR cells were highly resistant to doxorubicin. Compounds 1-4 induced an increase in the percentage of Annexin V-binding cells, indicating that 1-4 induced apoptosis in RAW 264.7 cells. Also, the condensation of nuclei, a characteristic morphological change of apoptosis, was observed in RAW 264.7 cells by the treatment with n-BuOH fraction, compounds 3 and 4, respectively.
Park
Jong Hyuk
JH
College of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Korea.
Kwak
Jong Hwan
JH
Khoo
Ja Heouk
JH
Park
Sung-Hoon
SH
Kim
Dae Up
DU
Ha
Dong Mun
DM
Choi
Sang Un
SU
Kang
Se Chan
SC
Zee
Ok Pyo
OP
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020128:Inhibitory Concentration 50; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D029623:Primulaceae / Q000737:chemistry*; D012503:Saponins / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D014315:Triterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D012503:Saponins; D014315:Triterpenes; D004317:Doxorubicin