Introduction: Gallic acid (GA) and curcumin (Cur) are natural phenolic compounds that their anti-tumor effects on many types of cancers have been proved. In the current study, the effect of the combination of these agents on MDA-MB-231 breast cancer cells was investigated. Methods: Inhibition of cell proliferation (MTT assay), light microscopy, fluorescence microscopy, cell cycle analysis, nitrite detection, ROS levels, measurement of the mitochondrial membrane potential, GSH level, Annexin V assay, RT-PCR and Western blotting methods were applied. Results: The results revealed the combination of GA and Cur strongly decreased MDA-MB-231 cell growth. Moreover, this combination increased ROS level and cytotoxic activity along with the glutathione depletion in MDA-MB-231 cells. Flow cytometry analysis showed the combination of GA and Cur increased sub-G1 cell population. Furthermore, fluorescent staining and Annexin V/PI assay showed that apoptotic cells were significantly increased in the presence of GA and Cur. At last, protein expression evaluation showed that the combination of GA and Cur significantly decreased Bcl-2 level while increased Bax, cleaved-caspase3 and PARP levels in MDA-MB-231 cells. Conclusion: These results suggest that GA in combination with Cur could be a possible candidate for chemoprevention agent of triple negative breast cancer.

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Actin and microtubules form cellular cytoskeletal network, which mediates cell shape, motility and proliferation and are key targets for cancer therapy. Changes in cytoskeletal organization dramatically affect mechanical properties of the cells and correlate with proliferative capacity and invasiveness of cancer cells. Changes in the cytoskeletal network expectedly lead to altered nonmechanical material properties including electrical conductivity as well. Here we applied, for the first time, microtubule and actin based electrical measurement to monitor changes in the electrical properties of breast cancer cells upon administration of antitubulin and anti-actin drugs, respectively. Semiconductive behavior of microtubules and conductive behavior of actins presented different bioelectrical responses (in similar frequencies) of the cells treated by anti-tubulin with respect to anti-actin drugs. Doped silicon nanowires were applied as the electrodes due to their enhanced interactive surface and compatibility with electronic fabrication process. We found that treatment with Mebendazole (MBZ), a microtubule destabilizing agent, decreases electrical resistance while treatment with Paclitaxel (PTX), a microtubule stabilizing agent, leads to an increase in electrical resistance. In contrast, actin destabilizing agents, Cytochalasin D (CytD), and actin stabilizing agent, Phalloidin, lead to an increased and decreased electrical resistance, respectively. Our study thus provides proof-of-principle of the usage of determining the electrical function of cytoskeletal compartments in grading of cancer as well as drug resistance assays.

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