A novel anti-tumor protein extracted from Meretrix meretrix Linnaeus induces cell death by increasing cell permeability and inhibiting tubulin polymerization.
Discovery and development of new pharmaceuticals from marine organisms are attracting increasing interest. Several agents derived from marine organisms are under preclinical and clinical evaluation as potential anti-cancer drugs. We extracted and purified a novel anti-tumor protein from the coelomic fluid of Meretrix meretrix Linnaeus by ammonium sulphate fractionation, ion exchange and hydrophobic interaction chromatography. The molecular weight of the highly purified protein, designated MML, was 40 kDa as determined by SDS-PAGE analysis. MML exhibited significant cytotoxicity to several cancer cell types, including human hepatoma BEL-7402, human breast cancer MCF-7 and human colon cancer HCT116 cells. However, no inhibitory effect was found when treating murine normal fibroblasts NIH3T3 and benign human breast MCF-10A cells with MML. The cell death induced by MML was characterized by cell morphological changes. The induction of apoptosis of BEL-7402 cells by MML was weak by DNA ladder assay. The possible mechanisms of its anti-tumor effect might be the changes in cell membrane permeability and inhibition of tubulin polymerization. MML may be developed as a novel, highly selective and effective anti-cancer drug.
Ning
Xuanxuan
X
Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, PR China.
Zhao
Jianmin
J
Zhang
Yuyan
Y
Cao
Subing
S
Liu
Ming
M
Ling
Peixue
P
Lin
Xiukun
X
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049872:Bivalvia / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D005591:Chemical Fractionation; D002852:Chromatography, Ion Exchange; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D045325:HCT116 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D008970:Molecular Weight; D041681:NIH 3T3 Cells; D011506:Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000302:isolation & purification / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011506:Proteins; D014404:Tubulin; D050257:Tubulin Modulators