BackgroundAdenine nucleotide translocase (ANT) is located in the inner mitochondrial membrane and catalyzes the exchange of mitochondrial ATP for cytosolic ADP. ANT has been known to be a major component of the permeability transition pore complex of mitochondria and contributes to mitochondria-mediated apoptosis. Human ANT has four isoforms (ANT1, ANT2, ANT3, and ANT4), and the expression of the ANT isoforms is variable depending on the tissue and cell type, developmental stage, and proliferation status. Among the isoforms, ANT1 is highly expressed in terminally-differentiated tissues, but expressed in low levels in proliferating cells, such as cancer cells. In particular, over-expression of ANT1 induces apoptosis in cultured tumor cells.MethodsWe applied an ANT1 gene transfer approach to induce apoptosis and to evaluate the anti-tumor effect of ANT1 in a nude mouse model.ResultsWe demonstrated that ANT1 transfection induced apoptosis of MDA-MB-231 cells, inactivated NF-κB activity, and increased Bax expression. ANT1-inducing apoptosis was accompanied by the disruption of mitochondrial membrane potential, cytochrome c release and the activation of caspases-9 and -3. Moreover, ANT1 transfection significantly suppressed tumor growth in vivo.ConclusionOur results suggest that ANT1 transfection may be a useful therapeutic modality for the treatment of cancer.

Background: There is a paucity of studies, as well as inconsistent findings, on the associations of homocysteine, folate, and vitamin B-12 with physical function and decline in older persons. Objective: We investigated the independent associations of homocysteine, folate, and vitamin B-12 with gait and balance performance and Instrumental Activities of Daily Living (IADL) in community-living older persons. Design: We performed cross-sectional analyses on baseline data of 796 respondents in the Singapore Longitudinal Ageing Study who had laboratory measurements of fasting homocysteine folate and vitamin B-12 and completed Performance Oriented Mobility Assessment (POMA) of gait and balance and self-reports of IADLs. Results: In multivariate analyses in which sex, age, education, housing type, comorbidities, hospitalization, depression and global cognitive scores, BMI, creatinine, arthritis and hip fracture, serum albumin and hemoglobin, and physical activities were controlled for, we showed that homocysteine, independently of folate and vitamin B-12, showed significant negative associations with POMA balance (P = 0.02), POMA gait scores (P , 0.01), and IADL (P , 0.01). Serum folate showed a significant positive association only with POMA balance scores (P , 0.045). No significant independent associations for vitamin B-12 were observed. Conclusions: The independent association of elevated homocysteine and low folate, but not vitamin B-12, on physical and functional decline was supported in this study. Interventional studies of the physical functional effects of folate and vitamin B-12 status in different populations are needed.Am J Clin Nutr 2012;96: 1362-8.

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The findings suggest that low levels of albumin and hemoglobin are potentially useful risk markers of physical functional decline in older adults. Further research should investigate whether improvements in the levels of albumin and hemoglobin alter the level of functional disability and risk of functional decline.

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