Abstract
BackgroundCell migration is involved in several pathological processes such as tumor invasion, neoangiogenesis and metastasis. Microtubules are needed in directional migration.MethodsTo investigate the effects of microtubule-binding agents (paclitaxel, vinblastine, colchicine, podophyllotoxin), benzophenanthridine alkaloids (sanguinarine, chelerythrine, chelidonine) and other anti-tumor drugs (homoharringtonine, doxorubicin) on cell migration, we performed the in vitro wound healing assay. The interactions between selected alkaloids and microtubules were studied via U2OS cells expressing microtubule-GFP markers.ResultsThe microtubule-binding natural products paclitaxel, vinblastine, colchicine and podophyllotoxin significantly altered microtubule dynamics in living cells and inhibited cell migration at concentrations below apparent cytotoxicity. The benzophenanthridine alkaloid sanguinarine, chelerythrine and chelidonine which affected microtubules in living cells, did not inhibit cell migration. Homoharringtonine (protein biosynthesis inhibitor) and doxorubicin significantly inhibited cell migration, however, they did not exert obvious effects on microtubules.ConclusionIn this study, we demonstrated that microtubule-binding agents are effective anti-migrating agents; moreover, homoharringtonine and doxorubicin can be referred as anti-migrating agents, but direct microtubule dynamics are not involved in their mode of action. Our study provides evidence that some alkaloids and other microtubule-binding natural products may be interesting candidates for the development of novel agents against metastasis.
Highlights
Cell migration is involved in several pathological processes such as tumor invasion, neoangiogenesis and metastasis
The benzophenanthridine alkaloids sanguinarine, chelerythrine and chelidonine are cytotoxic; they inhibited the growth of U2OS cells with IC50 values ranging between 0.92 μM and 3.86 μM
This study investigated the roles of cytotoxic alkaloids in biological processes related to cell migration and cytoskeleton dynamics
Summary
Cell migration is involved in several pathological processes such as tumor invasion, neoangiogenesis and metastasis. Wang et al BMC Pharmacology and Toxicology (2019) 20:4 cellular processes including intracellular transport, cell division and migration [14–16], making them attractive targets for natural toxins in cancer research [17, 18]. Microtubule-binding agents (MBAs) are important components in clinical combination chemotherapy and applied widely to treat many different kinds of cancers [19]. Alkaloids constitute the most important group of MBAs; well-known examples are the microtubule-stabilizer paclitaxel (a diterpene alkaloid from Taxus that clinically used in the treatment of Kaposi’s sarcoma, lung, ovarian and breast cancer) and the microtubule-destabilizer vinblastine (a vinca alkaloid from Catharanthus roseus that clinically applied for Bladder, lung and breast cancer, Hodgkin’s disease, solid tumors, leukaemia and lymphomas) [20, 21]. In the last few years, the targeting of cell migration has become a therapeutically challenging approach for cancer treatment and MBAs have been reported to inhibit cell migration by interfering with microtubule dynamics [22]
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