Enhanced Antiproliferation Potency of Electrical Pulse-Mediated Metformin and Cisplatin Combination Therapy on MDA-MB-231 Cells

Sahu, Praveen Kumar; Camarillo, Ignacio G.; Sundararajan, Raji

doi:10.1007/s12010-021-03723-5

Cited by 6 publications

(3 citation statements)

References 45 publications

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“…The action of ROS is found to be a double-edged sword; at lower levels, ROS increase cell proliferation [4], but at higher levels, cause cell death as reported in several studies [4,5]. Increased ROS-induced apoptosis has been reported in cancer cells, due to chemotherapy or radiation therapy, indicating the potential role of ROS modulation in anticancer combinational therapies [5][6][7]. It is found that photodynamic therapy is more suitable, which is based on the generation of ROS after stimulation by light.…”

Section: Introductionmentioning

confidence: 92%

Enhancement of reactive oxygen species production in triple negative breast cancer cells treated with electric pulses and resveratrol

Giri

Camarillo

Sundararajan

2023

Exploration of Targeted Anti-Tumor Therapy

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Aim: Triple negative breast cancer (TNBC) is difficult to treat since it lacks all the three most commonly targeted hormone receptors. Patients afflicted with TNBC are treated with platinum core chemotherapeutics, such as cisplatin. Despite the initial effective anticancer effects of cisplatin, TNBC attenuates its effect and develops resistance eventually, which results in tumor reoccurrence. Hence, there is a critical demand for effective, alternative, and natural ways to treat TNBC. Towards this, a promising technique for inhibiting TNBC cell proliferation involves promoting the production of reactive oxygen species (ROS), which triggers pro-apoptotic caspases 9 and 3. Resveratrol (RESV), an active bio compound found in naturally available fruits, such as grapes, is utilized in this research for that. In addition, electrochemotherapy (ECT), which involves the application of electrical pulses (EP), was utilized to enhance the uptake of RESV. Methods: MDA-MB-231, human TNBC cells were treated with/out RESV, and eight 600–1,000 V/cm, 100 μs pulses at 1 Hz. The cells were characterized by using various assays, including viability assay, and ROS assay. Results: A TNBC cell viability of as low as 20% was obtained at 24 h (it was 13% at 60 h), demonstrating the potential of this novel treatment. ROS production was the highest in the combination of EP at 1,000 V/cm along with RESV at 100 μmol/L. Conclusions: Results indicate that RESV has the potential as an anti-TNBC agent and that EP + RESV can significantly enhance the cell death to reduce MDA-MB-231 cell viability by increasing ROS production and triggering apoptosis.

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Section: Introductionmentioning

confidence: 92%

Enhancement of reactive oxygen species production in triple negative breast cancer cells treated with electric pulses and resveratrol

Giri

Camarillo

Sundararajan

2023

Exploration of Targeted Anti-Tumor Therapy

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“…Metformin, which is widely used as anti-diabetic drug, has demonstrated important anti-cancer effects both in vitro and in vivo in many studies [16][17][18]. Metformin combination with other treatment strategies has also been widely reported [19]. Metformin was demonstrated to enhance anti-cancer treatments for different cancer cell types through various mechanisms including mitochondrial apoptosis induction and inhibition of DNA synthesis [20].…”

Section: Ivyspring International Publishermentioning

confidence: 99%

Combination of Metformin and Sorafenib Induces Ferroptosis of Hepatocellular Carcinoma Through p62-Keap1-Nrf2 Pathway

Tang¹,

Chen²,

Liu³

et al. 2022

J. Cancer

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Hepatocellular carcinoma (HCC) is one of the most lethal cancers in the world. Sorafenib is the first small-molecule multi-kinase inhibitors approved by FDA for treatment of advanced HCC. Metformin has been demonstrated to have benefit for preventing cancer progression. In human recurrent HCCs, NF-E2-related factor 2 (Nrf2) was overexpressed and associated with poor survival. Nrf2 related signaling pathway plays central role to mediate cellular resistance to sorafenib through protecting HCC cells from ferroptosis. The effect of Combination treatment for HCC cells and the intrinsic mechanism have not been reported. In this study, metformin augmented the anti-tumor effect of sorafenib for HCC through ferroptosis induction by inhibiting Nrf2 related pathway. Based on the results of Nrf2 knockdown and p62 knockdown study, the combination of sorafenib and metformin suppressed proliferation of HCC cells through p62-Keap1-Nrf2/HO1 signaling way. Size of xenografts treated with the combination of sorafenib and metformin was smaller than other groups in vivo . Moreover, the combination treatment greatly induced ferroptosis in HCC cells through inhibiting Nrf2 expression. Based on our findings, the combination treatment suppressed proliferation of HCC cells through ferroptosis induction, by p62-Keap1-Nrf2/HO1 signaling way.

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“…Electroporation can minimize drug concentration and side effects on the surrounding tissues by improving drug efficacy [56]. Prior studies suggest that electroporation techniques can be effectively combined with various drugs to improve therapeutic efficacy [57][58][59][60][61]. This research examined the efficacy of a combination of Met with EP using various assays.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of metformin and electrical pulses in breast cancer MDA-MB-231 cells

Sahu,

Camarillo,

Sundararajan

2024

Exploration of Targeted Anti-Tumor Therapy

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Aim: Triple-negative breast cancer (TNBC) is a very aggressive subset of breast cancer, with limited treatment options, due to the lack of three commonly targeted receptors, which merits the need for novel treatments for TNBC. Towards this need, the use of metformin (Met), the most widely used type-2 diabetes drug worldwide, was explored as a repurposed anticancer agent. Cancer being a metabolic disease, the modulation of two crucial metabolites, glucose, and reactive oxygen species (ROS), is studied in MDA-MB-231 TNBC cells, using Met in the presence of electrical pulses (EP) to enhance the drug efficacy. Methods: MDA-MB-231, human TNBC cells were treated with Met in the presence of EP, with various concentrations Met of 1 mmol/L, 2.5 mmol/L, 5 mmol/L, and 10 mmol/L. EP of 500 V/cm, 800 V/cm, and 1,000 V/cm (with a pulse width of 100 µs at 1 s intervals) were applied to TNBC and the impact of these two treatments was studied. Various assays, including cell viability, microscopic inspection, glucose, ROS, and wound healing assay, were performed to characterize the response of the cells to the combination treatment. Results: Combining 1,000 V/cm with 5 mmol/L Met yielded cell viability as low as 42.6% at 24 h. The glucose level was reduced by 5.60-fold and the ROS levels were increased by 9.56-fold compared to the control, leading to apoptotic cell death. Conclusions: The results indicate the enhanced anticancer effect of Met in the presence of electric pulses. The cell growth is inhibited by suppressing glucose levels and elevated ROS. This shows a synergistic interplay between electroporation, Met, glucose, and ROS metabolic alterations. The results show promises for combinational therapy in TNBC patients.

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Enhanced Antiproliferation Potency of Electrical Pulse-Mediated Metformin and Cisplatin Combination Therapy on MDA-MB-231 Cells

Cited by 6 publications

References 45 publications

Enhancement of reactive oxygen species production in triple negative breast cancer cells treated with electric pulses and resveratrol

Enhancement of reactive oxygen species production in triple negative breast cancer cells treated with electric pulses and resveratrol

Combination of Metformin and Sorafenib Induces Ferroptosis of Hepatocellular Carcinoma Through p62-Keap1-Nrf2 Pathway

Efficacy of metformin and electrical pulses in breast cancer MDA-MB-231 cells

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