Cytotoxicity of natural extract from Tegillarca granosa on ovarian cancer cells is mediated by multiple molecules

Abstract

Purpose: 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, ?-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. Conclusion: HSS has a potential cytotoxic effect on human ovarian cancer cells, which was mediated by multiple signal molecules including bcl-2, caspase-3, ?-catenin, and CD24. These findings will provide a theoretical basis for HSS’s potential clinical application as a novel marine anti-cancer agent.

Tegillarca granosa Extract Haishengsu Induces Apoptosis in Human Hepatocellular Carcinoma Cell Line BEL-7402 Via Fas-Signaling Pathways

“…Tegillarca granosa, widely distributed in China, is one breed of seashell and has been used as traditional Chinese seafood for hundreds of years [17]. Haishengsu (HSS) is an extract isolated from T. granosa, and its major chemical constituents are proteins with a molecular weight ranging from 15 to 23 kDa.…”

Haishengsu, a Protein from Shellfish Tegillarca L. granosa, Inhibits the Growth and the Activity of Matrix Metalloproteinases-2 and -9 in Human Lung Carcinoma

“…4,5 The molecular weight of HSS is approximately 15 kDa (15-23 kDa). HSS was dissolved in phosphate-buffered saline before use.…”

“…Further examination revealed that the inhibition of HSS on human leukemia cells K562 was mediated through the induction of apoptosis and cell cycle arrest. [4][5][6] The apoptotic proteins of bax and caspase-3 were increased and bcl-2 was decreased in K562 and K562/A02 cells following HSS treatment. 21 HSS has been considered as a potential candidate agent for cancer treatment, and phase I clinical evaluation on several types of cancers is currently underway in China.…”

“…We found that HSS had substantial inhibitory effects on several types of cancer cells, including human ovarian cancer cells SKOV-3 and OVCAR-3 and human leukemic cells K562 and its multidrug resistance (MDR) counterpart K562/A02 cells. [4][5][6] However, the inhibitory effect of HSS on tumor invasion and metastasis has not been thoroughly investigated.…”

“…[1][2][3] Recently, the biological activities of several proteins purified from T. L. granosa have been evaluated in vitro and in vivo. 4,5 We isolated a novel seashell protein with a molecular weight of approximately 15 kDa (15-23 kDa) from T. L. granosa and named it Haishengsu (HSS). We found that HSS had substantial inhibitory effects on several types of cancer cells, including human ovarian cancer cells SKOV-3 and OVCAR-3 and human leukemic cells K562 and its multidrug resistance (MDR) counterpart K562/A02 cells.…”