AI Article Synopsis
- * After 24 hours, MEN+D treatment reduced mitochondrial respiration, leading to decreased ATP production and efficiency, while longer treatments (48-96 hours) also showed enhanced anti-proliferative effects with the combined drugs.
- * The combination therapy increased oxidative stress markers and altered mitochondrial function, indicating that it may be more effective in targeting cancer compared to individual treatments, potentially due to its effects on cell metabolism and autophagy.
Article Abstract
The aim of this study was to determine new insights into the molecular mechanisms involved in the antiproliferative action of menadione + calcitriol (MEN+D) on MCF-7 cells. After 24 h, MEN+D inhibited the cell growth but was not observed with each single treatment. The combined drugs reduced the mitochondrial respiration at that time, as judged by an increase in the proton leak and a decrease in the ATP generation and coupling efficiency. At longer times, 48 or 96 h, either D or MEN reduced the proliferation, but the effect was higher when both drugs were used together. The combined treatment increased the superoxide anion ([Formula: see text]) and nitric oxide (NO) contents as well as acidic vesicular organelles (AVOs) formation. The percentage of cells showing the lower mitochondrial membrane potential (ΔΨ) was highly increased by the combined therapy. LC3-II protein expression was enhanced by any treatment. In conclusion, the antiproliferative action of MEN+D involves oxidative/nitrosative stress, mitochondrial alteration, and autophagy. This combined therapy could be useful to treat breast cancer cells because it inhibits multiple oncogenic pathways more effectively than each single agent.
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| http://dx.doi.org/10.1139/cjpp-2019-0585 | DOI Listing |
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