Untitled

Abstract

The effects of trivalent metal ions such as lanthanoid (La3+, Ce3+, Nd3+, Sm3+, Gd3+, Er3+, Yb3+, Lu3+) and Al3+ ions on the morphological change and proliferation of B16 melanoma cells in culture are discussed. These metal ions induced morphological transformations and decreased growth rates at doses of 1 mM. B16 melanoma cells treated with La3+, Ce3+, Nd3+, Sm3+, and Gd3+ showed polyhedrical spreading. Elongation of axones was dependent on the metal ions. B16 melanoma cells treated with Er3+, Yb3+, Lu3+, and Al3+ showed a long slender shape. Growth rates of melanoma cells in the presence of 1 mM of metal ions (La3+, Ce3+, Nd3+, Sm3+, Gd3+, Yb3+, Al3+) were significantly lower than that of control cells. Measurements of cell cycle indicated that the metal ions arrested the transitions from G0/G1 to S state.

New Insights into the Chemistry of the Antineoplastic Lanthanum Complex Tris(1,10‐phenanthroline)tris(thiocyanato‐κN)lanthanum(III) (KP772) and Its Interaction with Biomolecules

“…[2,3] Therefore, such compounds are able to inhibit calcium fluxes, required for cell cycle regulation, but they cannot only substitute for calcium but also for other metal ions such as Mg 2+ , Fe 3+ and Mn 2+ in proteins, leading to the inhibition of their functions. [4,5] The tumor-inhibiting activity of lanthanum is considerably enhanced by complexation with various ligands such as phenanthroline derivatives. [6] Phenanthroline induces a cell cycle arrest in G 0 /G 1 , most likely based on its metal-chelating ability.…”

Gadolinium promoted proliferation and enhanced survival in human cervical carcinoma cells

“…The dual effects of lanthanides were discussed on the basis of bi-directional dose dependence (Wang et al 1999). The proapoptosis effect frequently appeared at the concentration higher up to millimolar levels (Mizgerd et al 1996;Sato et al 1998;Greisberg et al 2001;Dai et al 2002;Shi and Huang 2005), while proliferative effect often occured at micromolar concentration (Yu et al 2005(Yu et al , 2006Fu et al 2008).…”

“…Thirdly, many previous studies investigated the cytotoxic effects of lanthanides on cancer cells (Mizgerd et al 1996;Sato et al 1998;Greisberg et al 2001;Dai et al 2002;Shi and Huang 2005). These studies usually used species such as chlorides, nitrates or acetates of lanthanides (III).…”

A Novel Cytotoxic Cerium Complex: Aquatrichloridobis(1,10‐phenanthroline)cerium(III) (KP776). Synthesis, Characterization, Behavior in H2O, Binding towards Biomolecules, and Antiproliferative Activity

“…-The very interesting biological properties of lanthanides are primarily based on their similarity to calcium: Ln 3 þ ions have a high affinity for Ca 2 þ binding sites in biomolecules because of their similar ionic radii, but higher charge [1] [2]. Therefore, simple lanthanum(III) salts are able to inhibit calcium fluxes, which are required for cell-cycle regulation, but lanthanides can also substitute for calcium and other metal ions such as Mg 2 þ , Fe 3 þ , and Mn 2 þ in metalloenzymes, leading to the inhibition of their functions [3] [4]. Especially cerium compounds have been wellknown for their pharmacological properties since the 18th century and cerium(III) iodide was applied intravenously for the treatment of lymphogranulomatosis or inoperable solid tumors in the pioneering era of cancer chemotherapy in the 1920s [5].…”

“…This medication induced shrinkage of the tumor and improved the quality of life in several cases of locally advanced or metastatic tumors of different origin [6] [7]. The antiproliferative effects are associated with morphological changes and a cell-cycle arrest in G 0 /G 1 [8]. Evaluation of Ce III complexes with 2,2'-bipyridine, 1,10-phenanthroline, and related ligands revealed those with 1,10-phenanthroline as the most promising [5].…”