Cytotoxicity of neolignans identified in Saururus chinensis towards human cancer cell lines.
The cytotoxicity of compounds derived from the aerial parts of Saururus chinensis towards 24 cancer model and six normal cell lines was examined by MTT assay and compared with those of the anticancer agents cisplatin and doxorubicin. The active principles were characterized as the neolignans manassantin A, and its erythro, erythro- and threo, erythro-epimers by spectroscopic analysis. Manassantin A was isolated from S. chinensis as a new cytotoxic principle. Its two epimers were isolated for the first time in nature. The neolignans were more active than cisplatin and doxorubicin, with IC50 values of the neolignans, cisplatin, and doxorubicin against SK-Hep-1, PC-3, DU-145, BT-20, SK-BR-3, T-47D, Hela, T98G, and SK-MEL-28 cancer cell lines, in the ranges 0.018-0.423, 1.175-7.922, and 0.131- >50 microg/mL, respectively. Manassantin A and its threo, erythro-epimer were equicytotoxic towards model cancer cell lines. threo, erythro-Manassantin A was more active than erythro, erythro-manassantin A. Additionally, these three neolignans (IC50 > 10 microg/mL) had very low cytotoxicity towards six normal cell lines, whereas cisplatin (IC50 2.846-0.825 microg/mL) and doxorubicin (IC50 5.222-0.008 microg/mL) exhibited potent cytotoxic effects. Structure-activity relationships indicate that the hydroxy moiety appears to be essential for cytotoxicity. These neolignans merit further study as potential anticancer agents or as leads.
Hahm
Jong-Cheon
JC
GN R&D Center, GreenTek21 Co., Sungnam, Republic of Korea.
Lee
In-Kyoung
IK
Kang
Won-Ki
WK
Kim
Soo-Un
SU
Ahn
Young-Joon
YJ
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008517:Phytotherapy; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D032134:Saururaceae; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D004317:Doxorubicin; D002945:Cisplatin