Antitumor activity of Pulsatilla koreana saponins and their structure-activity relationship.
Seventeen saponins isolated from the root of Pulsatilla koreana were examined for their in vitro cytotoxic activity against the human solid cancer cell lines, A-549, SK-OV-3, SK-MEL-2, and HCT15, using the SRB assay method, and their in vivo antitumor activity using BDF1 mice bearing Lewis lung carcinoma (LLC). The saponins 5-17, with a free acidic functional group at C-28 of aglycon, exhibited moderate to considerable cytotoxic activity, however, the saponins 1-4, esterified with a trisaccharide at C-28 of aglycon, did not exhibit cytotoxic activity (ED50; >300 microM). Among them, oleanolic acid 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->4)]-alpha-L-arabinopyranoside (10) exhibited the most potent cytotoxic activity (ED50; 2.56, 2.31, 1.57, 8.36 microM, respectively). In vivo test, hederagenin 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->4)]-alpha-L-arabinopyranoside (6, Inhibition Ratio, IR; 66.9%) exhibited more potent antitumor activity than taxol (IR; 35.8%) and doxorubicin (IR; 62.1%). Also, hedragenin 3-O-beta-D-glucopyranosyl-(1-->4)-O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside (17, IR; 50.3%) exhibited potent antitumor activity. These two saponins were identically comprised of a hederagenin aglycon moiety and a sugar sequence O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside at C-3 of the hederagenin, suggesting that the two elements are essential factors for the antitumor activity.
Bang
Seong-Cheol
SC
SB Pharmaceutical Co., Chungnam, Korea.
Lee
Ji-Hyun
JH
Song
Gyu-Yong
GY
Kim
Dong-Hee
DH
Yoon
Mi-Young
MY
Ahn
Byung-Zun
BZ
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D051379:Mice; D018517:Plant Roots / Q000737:chemistry; D031946:Pulsatilla / Q000737:chemistry*; D012503:Saponins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D012503:Saponins