Targeted cellular ionic calcium chelation by oxalates: Implications for the treatment of tumor cells

Abstract

BackgroundIn malignant melanoma, it has been published that up to 40% of cancer patients will suffer from brain metastasis. The prognosis for these patients is poor, with a life expectancy of 4 to 6 months. Calcium exchange is involved in numerous cell functions. Recently, three types of cellular calcium sequestration have been reported in the medical literature. The first describes a transgenic mouse model in which an increase of aberrant calcium channels triggers hypertrophy and apoptosis. The second provides a protective mechanism whereby astrocytes in the brain inhibit apoptosis of tumor cells by moving ionic calcium out of the tumor cells thru gap junctions. The third is via calcium chelation, which causes cell apoptosis by converting ionic calcium into a calcium salt. This process has been shown to operate in atrial myocardial cells, thus not allowing the intracellular calcium stores to flow through the myocytes intercalated discs. Ideally chemotherapeutic agents would be those that initiate apoptosis in tumor cells.Presentation of the HypothesisWe hypothesize that the recent reported intracellular calcium sequestration by oxalate chelation, due to its chemical process of converting ionic calcium into a calcium salt, may inhibit the protective effect of astrocytes on brain tumor metastasized melanoma cells by not allowing free calcium to leave the metastatic cells, simultaneously apoptosis of tumor and some healthy adjacent cells could occur. This hypothesis could be extended to include other cancerous tumors such as skin cancers amongst others.Testing the hypothesisUsing the experimental model showing the protective mechanism of co-cultured reactive astrocytes and tumor cells treated with oxalates could be used to test this hypothesis in vitro. The calcium specific von Kossa technique could be used to confirm the presence of chelated intracellular calcium architecture of the metastatic cells (which is a sign of apoptosis), and extracellular calcium chelation stores of the Astrocytes (which has been shown to slow neural conduction).Implications of the HypothesisThe life expectancy in patients with metastasized malignant melanoma brain tumors could be significantly prolonged if the chemotherapeutic issue of brain metastasis is overcome. Other cancerous tumors can also be treated by this Targeted Chelation Approach. Ionic calcium sequestration using naturally occurring calcium chelators, viz., oxalates, could accomplish this desired outcome.

Chemotherapy-induced peripheral neuropathy—part 2: focus on the prevention of oxaliplatin-induced neurotoxicity

“…Oxalate is a well-known calcium chelator [13], and oxalate-induced pain is regarded as a consequence of the chelation of extracellular calcium ions (i.e., the removal of extracellular calcium ions), which in turn leads to the increase in sodium conductance, neuronal depolarization and hyperexcitability ( Fig. 1) [14,15].…”

Synthesis, anticonvulsant, and antinociceptive activity of new 3‐(3‐methyl‐2,5‐dioxo‐3‐phenylpyrrolidin‐1‐yl)propanamides and 3‐phenyl‐butanamides

“…[ 33 ] During this acute phase, neurotoxicity induced by oxaliplatin is perceived to be due to the accumulation of its metabolite, oxalate, which acts as a calcium chelator, indirectly altering the kinetics of calcium‐sensitive VGSCs. [ 32,34 ] In contrast to this, chronic peripheral neuropathy after oxaliplatin treatment is mainly due to a permanent distal sensory loss, the death of sensory neurons, and nerve cell necrosis, which all result from binding of oxaliplatin to mitochondrial DNA. [ 29,35 ] As shown in Figure 3, compound 6 reduced cold allodynia mainly in the acute phase of neuropathy, which suggests its potential action through VGSCs, VGCCs, or other types of ion channels.…”

Modular Small Diameter Vascular Grafts with Bioactive Functionalities

“…Finally biosilica is assessable to the carbonic anhydrases, a family of enzymes that is related to sponge-specific silicase [ 93 ]. The removal of Ca 2+ from the “stabile” polymer complexes within the universal scaffold might be achieved by oxalate chelation [ 94 ] as well by organic polymers in the extracellular environment [ 95 ]. This property of bTEBV to be prone to metabolic turnover might open the door for an inclusion of the bTEBV in the physiological regeneration of the vessel walls.…”