Antitumor principle constituents of Myrica rubra Var. acuminata.
Myrica rubra var. acuminata is a native shrub widely distributed and used as folk medicine in Taiwan for stomach disorders and diarrhea. Column chromatography combined with cytotoxic bioassay-guided fractionation was performed to isolate the antitumor principles from fresh leaves of M. rubravar. acuminata. The 20% MeOH eluate fraction of M. rubra var. acuminata inhibited the viability of HeLa and P-388 cells in an in vitro assay and an in vivo P-388 tumor-bearing CDF(1) mouse model. The percent increase in life span (%ILS) of 20% MeOH eluate fraction was greater than 125%. (-)-Epigallocatechin 3-O-gallate (1) and prodelphinidin A-2,3'-O-gallate (2) were isolated from D-20 as the antitumor principle components. Both compounds can inhibit the growth of HeLa cells, but 1 had lower cytotoxic effects in normal cervical fibroblasts than did 2. Moreover, pretreatment with a caspase-3 specific inhibitor prevented 1- and 2-induced poly(ADP-ribose) polymerase cleavage. In view of these results, we suggest that 1 and 2 can induce apoptosis in HeLa cells and that activation of caspase-3 may provide a mechanistic explanation for their cytotoxic effects. Therefore, we suggest that the 20% MeOH eluate fraction extract is good for health and that M. rubra var. acuminata is an economically valuable plant.
Yang
Ling-Ling
LL
Graduate Institute of Pharmacognosy, Taipei Medical University, 250 Wu-Hsing Street, Taipei 110, Taiwan, Republic of China.
Chang
Chia-Chen
CC
Chen
Lih-Geeng
LG
Wang
Ching-Chiung
CC
D000818:Animals; D000872:Anthocyanins / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002584:Cervix Uteri / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D000432:Methanol; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008875:Middle Aged; D031641:Myrica / Q000737:chemistry*; D009368:Neoplasm Transplantation; D010936:Plant Extracts / Q000737:chemistry; D018515:Plant Leaves / Q000737:chemistry*
D000872:Anthocyanins; D000970:Antineoplastic Agents; D010936:Plant Extracts; C472180:prodelphinidin B-2 3'-O-gallate; D002392:Catechin; C045651:epigallocatechin gallate; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D000432:Methanol