Allicin inhibits cell polarization, migration and division via its direct effect on microtubules.
Allicin (diallyl thiosulfinate) is a major biologically active component of garlic that is known to inhibit cell proliferation and induce apoptosis. The effects of allicin are attributed to its ability to react with thiol groups. However, the mechanism underlying the cytostatic activity of allicin, as well as the identity of the relevant subcellular targets, are not known. In the present study, we found that the effects of allicin on cell polarization, migration, and mitosis are similar to the effects of microtubule-depolymerizing drugs such as nocodazole. Moreover, treatment of cultured fibroblasts with micromolar doses of allicin results in microtubule depolymerization in cells within minutes of its application, without disrupting the actin cytoskeleton or inducing direct cytotoxic effects. Furthermore, allicin blocks the polymerization of pure tubulin in vitro in a concentration-dependent manner, suggesting that it acts directly on tubulin dimers. Sulfhydryl (SH)-reducing reagents such as 2-mercaptoethanol and dithiothreitol abolish the effect of allicin on microtubule polymerization. Thus, allicin is a potent microtubule-disrupting reagent interfering with tubulin polymerization by reaction with tubulin SH groups.
Prager-Khoutorsky
Masha
M
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Goncharov
Igor
I
Rabinkov
Aharon
A
Mirelman
David
D
Geiger
Benjamin
B
Bershadsky
Alexander D
AD
D000199:Actins / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D016764:Cell Polarity / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects; D004220:Disulfides; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D005737:Garlic / Q000737:chemistry; D007091:Image Processing, Computer-Assisted; D007211:Indoles; D051379:Mice; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D008870:Microtubules / Q000187:drug effects*; D041681:NIH 3T3 Cells; D015739:Nocodazole / Q000494:pharmacology; D013441:Sulfinic Acids / Q000494:pharmacology*; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism
D000199:Actins; D000970:Antineoplastic Agents; D004220:Disulfides; D005456:Fluorescent Dyes; D007211:Indoles; D013441:Sulfinic Acids; D014404:Tubulin; C006452:allicin; C007293:DAPI; D015739:Nocodazole