Cytotoxicity of natural extract from Tegillarca granosa on ovarian cancer cells is mediated by multiple molecules.
OBJECTIVE
To determine the cellular and molecular mechanism of cytotoxicity induced by Haishengsu (HSS), nature extract from Tegillarca granosa, toward human ovarian cancer cell lines SKOV-3 and OVCAR-3.


METHODS
The cytotoxic effects of HSS on two ovarian cancer cell lines were tested by XTT assay. Cell apoptosis and cell cycle arrest induced by HSS were demonstrated by DNA ladder assay and flow cytometric analysis, respectively. RT-PCR or flow cytometric analysis was used to investigate the expression of bcl-2, caspase-3, p53, beta-catenin, E-cadherin, CD24, and CD44.


RESULTS
Continuous exposure to HSS for 48 h produced cytotoxic effects on both cell lines in a concentration dependent manner, which was accompanied by apoptosis and cell cycle arrest. Apoptosis associated gene bcl-2 and caspase-3, tumor metastasis associated gene ?-catenin, but not E-cadherin, and CD24, but not CD44, were involved in the effect of growth inhibition induced by HSS. Although p53 mediated apoptosis induced by HSS in OVCAR-3 cells, it was not required in SKOV-3 cells.


CONCLUSIONS
HSS has a potential cytotoxic effect on human ovarian cancer cells, which was mediated by multiple signal molecules including bcl-2, caspase-3, beta-catenin, and CD24. These findings will provide a theoretical basis for HSS's potential clinical application as a novel marine anti-cancer agent.
Yonsei University College of Medicine, Seoul, South Korea.
Ming-Qing
MQ
Gao
Yan-Tao
YT
Han
Li
L
Zhu
Shou-Guo
SG
Chen
Zhen-Yu
ZY
Hong
Chun-Bo
CB
Wang
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D049893:Arcidae / Q000737:chemistry*; D051927:CD24 Antigen / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D000970:Antineoplastic Agents; D051927:CD24 Antigen; D018960:Hyaluronan Receptors; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D053148:Caspase 3