Are mitochondria a potential target for anti-cancer therapy in carcinoid tumors?

摘要

Gastrointestinal (GI) carcinoids are slow growing malignancies of neuroendocrine phenotype that can behave aggressively. To date, there are no effective therapies for metastatic carcinoid cancer. Previous work by our lab and others has shown that carcinoids express variety of voltage-operated (VOCCs) and non-voltage-operated Ca2+ channels to allow Ca 2+ to enter the cell. Although, the role of Ca2+ entry in these tumors is not well understood, previous work by our group and others has shown that mitochondria are important regulators of voltage-operated and non-voltage-operated Ca2+ entry. In addition, cancer cells typically exhibit mitochondrial dysfunction and poor anti-oxidant status. These observations and the central role that mitochondria play in metabolism, Ca2+ homeostasis and cell death pathways make mitochondria an appealing potential target for anti-cancer treatment in carcinoid tumors. We used an spectrum of human cancer cell lines and a variety of microfluorescence methods including wide-field, confocal, and total internal reflection (TIRF) microscopy to assess Ca2+ signaling and mitochondrial function in combination with pharmacological interventions to assay whether mitochondria are a iv potential target for anti-cancer therapy. To this end, we tested the effectiveness of an oxidant therapy approach in carcinoid cells.