Biophysical mechanism for zinc as an anticancer agent.

The experimental observation that an increase in calcium above micromolar concentrations results in a slowing or stopping of anaphase-A motion is evidence for an electrostatic mechanism for poleward mitotic chromosome motions. Specifically, higher concentrations of doubly-charged calcium ions screen negative charges at microtubule free "plus" ends at kinetochores and at centrosomes. These structures normally interact with positive charges at kinetochores and positively charged microtubule free ends vicinal to centrosomes to generate poleward force. As with calcium ions, doubly-charged zinc cations can also shield these negative charges, thereby interfering with force generation for anaphase-A chromosome motion, aborting mitosis. Experimental evidence reveals that dysregulation of free cytosolic zinc homeostasis contributes to cancerous transformation. Treatment of cancers by increasing zinc concentration has unknowingly been accomplished by utilizing zinc ionophores to facilitate zinc transport across the plasma membrane, revealing an inverse relationship between malaria incidence - and malaria treatment with zinc ionophores - and cancer mortality. Here we hypothesize a biophysical mechanism for cancer therapy employing zinc supplementation enhanced by zinc ionophores.

Erratum to: Electrostatic forces drive poleward chromosome motions at kinetochores.

[This corrects the article DOI: 10.1186/s13008-016-0026-1.].

Electrostatic forces drive poleward chromosome motions at kinetochores.

BACKGROUND: Recent experiments regarding Ndc80/Hec1 in force generation at kinetochores for chromosome motions have prompted speculation about possible models for interactions between positively charged molecules at kinetochores and negative charge at and near the plus ends of microtubules. DISCUSSION: A clear picture of how kinetochores and centrosomes establish and maintain a dynamic coupling to microtubules for force generation during the complex motions of mitosis remains elusive. The current paradigm of molecular cell biology requires that specific molecules, or molecular geometries, for force generation be identified. However, it is possible to explain several different mitotic motions-including poleward force production at kinetochores-within a classical electrostatics approach in terms of experimentally known charge distributions, modeled as surface and volume bound charges interacting over nanometer distances. CONCLUSION: We propose here that implicating Ndc80/Hec1 as a bound volume positive charge distribution in electrostatic generation of poleward force at kinetochores is most consistent with a wide range of experimental observations on mitotic motions, including polar production of poleward force and chromosome congression.