Irreversible electroporation: a drug-free cancer treatment

Sundararajan, Raji; Salameh, Therese S.; Camarillo, Ignacio G.; Prabu, R. Raja; Natarajan, Arutselvan; Kannan, Sankaranarayanan

doi:10.1533/9781908818294.219

Cited by 8 publications

(10 citation statements)

References 11 publications

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“…MCF-7 cells, kindly provided by Dr. Suhad Ali (Department of Medicine, Cancer Research Program, McGill University Health Center, Canada), were cultured on plastic substratum in Dulbecco’s modified Eagle’s medium supplemented with 100 U/mL penicillin/streptomycin and 10% fetal bovine serum. The cells were maintained at 37 °C in a humidified 5% CO 2 incubator . Other MCF-7 cells were purchased from (VACSERA, Giza, Egypt) and maintained in RPMI medium with 4 mM sodium pyruvate, 4 mM l -glutamine, 100 U/mL penicillin/streptomycin, and 2.5% bovine serum albumin (BSA).…”

Section: Methodsmentioning

confidence: 99%

“…The cells were maintained at 37 °C in a humidified 5% CO 2 incubator. 52 Other MCF-7 cells were purchased from (VACSERA, Giza, Egypt) and maintained in RPMI medium with 4 mM sodium pyruvate, 4 mM Lglutamine, 100 U/mL penicillin/streptomycin, and 2.5% bovine serum albumin (BSA). The cells were incubated at 37 °C in a humidified 5% CO 2 incubator and were regularly checked for mycoplasma contamination.…”

Section: Acsmentioning

confidence: 99%

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Regulation of Autophagy Progress via Lysosomal Depletion by Fluvastatin Nanoparticle Treatment in Breast Cancer Cells

et al. 2020

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Fluvastatin (FLV) is a statin family member that may play a role in modulating a variety of medical disorders such as atherosclerosis and breast cancer. The present study addresses the ability of FLV to modulate the cellular immune response and provides a new nanosized FLV formula (self-nanoemulsifying delivery system, SNED) potentially more effective for suppression of breast cancer development. We monitored autophagic machinery through the expression of microtubule-associated protein 1A/1B-light chain 3 (LC3I/II). Lysosomal activity upon treatment was evaluated by mRNA and protein expression of lysosomal-associated membrane protein 1 (LAMP-1). Mitogen-activated protein kinase (MAPK) signaling and its association with proinflammatory cytokine secretion were assessed in treated cells. Autophagosome formation was significantly increased in cells that were pretreated with FLV-SNED in comparison to FLV-treated cells. Activation of autophagy was accompanied with arrest of LAMP-1 expression, which correlates with lysosomal activity. Simultaneously, both FLV and FLV-SNED activated MAPK signaling and modified interleukin-6 and tumor necrosis factor-α levels in treated cells. These findings indicate that FLV reduces cell viability via depletion of lysosomal activities along with accumulation of autophagosomes leading to disturbance of autophagosome-lysosomal fusion in treated cells. Furthermore, our data reveal the effectiveness of both FLV agents in the modulation of proinflammatory cytokine secretion from treated cells via regulation of MAPK signaling cascades and indicate that FLV-SNED is more efficient than FLV. This study provides new insights into how FLV regulates breast cancer cell viability via modulation of AMPK-mTOR and ERK-mTOR signaling, and through autophagosome formation accompanied by lysosomal degradation.

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Section: Methodsmentioning

confidence: 99%

Section: Acsmentioning

confidence: 99%

Regulation of Autophagy Progress via Lysosomal Depletion by Fluvastatin Nanoparticle Treatment in Breast Cancer Cells

et al. 2020

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“…Recently, Candeil et al (22) have reported that resistance to SN38 is the result of increased expression of ABC-family proteins. Other study suggested that electrical stimulations impair the translocation of MDR proteins to their functional locations at the plasma membrane (38). Thus, EP can increase the intracellular delivery of substances and decrease the efflux rate via their transporters.…”

Section: Effects Of Sn38 Electroporation and Their Combination On Cel...mentioning

confidence: 98%

Redox-related Molecular Mechanism of Sensitizing Colon Cancer Cells to Camptothecin Analog SN38

et al. 2020

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Background/Aim: The aim of this study was to elucidate the possibility of sensitizing colon cancer cells to the chemotherapeutic drug SN38 and investigate its mechanism of action after combined treatment with electroporation (EP). Materials and Methods: Cells were treated with SN38, EP and their combination for 24/48 h. The cell viability, actin cytoskeleton integrity, mitochondrial superoxide, hydroperoxides, total glutathione, phosphatidyl serine expression, DNA damages and expression of membrane ABC transporters were analyzed using conventional analytical tests. Results: The combination of EP and SN38 affected cell viability and cytoskeleton integrity. This effect was accompanied by: (i) high production of intracellular superoxide and hydroperoxides and depletion of glutathione; (ii) increased DNA damage and apoptotic/ ferroptotic cell death; (iii) changes in the expression of membrane ABC transporters -up-regulation of SLCO1B1 and retention of SN38 in the cells. Conclusion: The anticancer effect of the combined treatment of SN38 and EP is related to changes in the redox-homeostasis of cancer cells, leading to cell death via apoptosis and/or ferroptosis. Thus, electroporation has a potential to increase the sensitivity of cancer cells to conventional anticancer therapy with SN38.Colorectal cancer is one of the most aggressive cancers (1). It is a widespread malignant disease in industrialized countries. The clarification of its mechanism and the development of new therapeutic methods and techniques are of great interest nowadays.Chemotherapy with the semisynthetic pro-drug irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin; CPT-11) is one of the common therapeutic strategies in colorectal cancer. In 1996, irinotecan was approved for clinical use both in the United States and Japan (2, 3). So far, it is widely used in first-and second-line treatment of advanced colorectal cancer. Irinotecan is a water-soluble camptothecin analogue -alkaloidal derivative from Chinese tree plant (Camptotheca acuminata) (4). Bioactivation of CPT-11 in cells to its active metabolite SN38 is performed via a carboxylesterase-catalyzed reaction (4). SN38 has a 100-to 1,000-fold greater anticancer activity than irinotecan (4, 5). Furthermore, SN38 is a potent DNA topoisomerase I (Topo-I) inhibitor, acting via formation of a stable Topo-I-DNA cleavable complex, subsequently causing DNA damage (resulting in cell cycle arrest and/or cell death by apoptosis) (4).It is widely accepted that apoptosis is an energy-dependent process, which is characterized by early release of mitochondrial cytochrome c; activation of apoptotic protease activating factor 1 (APAF-1); and activation of caspase-9, ending with degradation of cellular proteins, such as PARP, laminin, and β-actin (hallmarks for programmed cell death). Induction of apoptosis is dependent on the cellular redoxstatus, which is essential for cell viability. Cellular redoxstatus is defined as a balance between the main endogenous

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“…nsPEF generators have many applications, including use in laser technologies, high speed photography, ultra-wideband radar detection and wireless communication systems to name but a few [1]- [7]. One growing application of nsPEFs is nanoelectroporation of biological cells to cause cell apoptosis for focus tumor ablation without causing damage to the extracellular matrix [3]- [7].…”

Section: Introductionmentioning

confidence: 99%

“…Literature suggests that nsPEF or nanosecond electroporation has potential for cell manipulation and control of cell physiology. Effects include increased plasma permeability of the cell membrane, allowing chemicals, drugs, or DNA to be introduced into the cell, calcium (Ca++) release, ion channel activation and apoptosis induction [3]- [7].…”

Section: Introductionmentioning

confidence: 99%

Generating Bipolar nsPulsed Electric Field using Transmission Line & Avalanche Transistors

Davies

Hancock

2021

2020 50th European Microwave Conference (EuMC)

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Irreversible electroporation: a drug-free cancer treatment

Cited by 8 publications

References 11 publications

Regulation of Autophagy Progress via Lysosomal Depletion by Fluvastatin Nanoparticle Treatment in Breast Cancer Cells

Regulation of Autophagy Progress via Lysosomal Depletion by Fluvastatin Nanoparticle Treatment in Breast Cancer Cells

Redox-related Molecular Mechanism of Sensitizing Colon Cancer Cells to Camptothecin Analog SN38

Generating Bipolar nsPulsed Electric Field using Transmission Line & Avalanche Transistors

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