Reactive oxygen species (ROS): Critical roles in breast tumor microenvironment

Malla, Rama Rao; Surepalli, Nagalakshmi; Farran, Batoul; Malhotra, Sanjay V.; Nagaraju, Ganji Purnachandra

doi:10.1016/j.critrevonc.2021.103285

Cited by 52 publications

(48 citation statements)

References 118 publications

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“…Importantly, the threshold for achieving an irreversibly damaging level of oxidative stress would depend on the basal metabolic rate and the existing inflammatory status of the recipient cells. Cancers characterized by elevated metabolic rates might hence be preferentially susceptible to PEMF-induced metabolic catastrophe ( 8 , 9 ). Accordingly, exposure to 3 mT PEMFs for one hour was previously shown to be cytotoxic to MCF-7 breast cancer cells, whereas the same exposure paradigm was tolerated by MCF10A nonmalignant breast cells ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Modulated TRPC1 Expression Predicts Sensitivity of Breast Cancer to Doxorubicin and Magnetic Field Therapy: Segue Towards a Precision Medicine Approach

et al. 2022

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Chemotherapy is the mainstream treatment modality for invasive breast cancer. Unfortunately, chemotherapy-associated adverse events can result in early termination of treatment. Paradoxical effects of chemotherapy are also sometimes observed, whereby prolonged exposure to high doses of chemotherapeutic agents results in malignant states resistant to chemotherapy. In this study, potential synergism between doxorubicin (DOX) and pulsed electromagnetic field (PEMF) therapy was investigated in: 1) MCF-7 and MDA-MB-231 cells in vitro; 2) MCF-7 tumors implanted onto a chicken chorioallantoic membrane (CAM) and; 3) human patient-derived and MCF-7 and MDA-MB-231 breast cancer xenografts implanted into NOD-SCID gamma (NSG) mice. In vivo, synergism was observed in patient-derived and breast cancer cell line xenograft mouse models, wherein PEMF exposure and DOX administration individually reduced tumor size and increased apoptosis and could be augmented by combined treatments. In the CAM xenograft model, DOX and PEMF exposure also synergistically reduced tumor size as well as reduced Transient Receptor Potential Canonical 1 (TRPC1) channel expression. In vitro, PEMF exposure alone impaired the survival of MCF-7 and MDA-MB-231 cells, but not that of non-malignant MCF10A breast cells; the selective vulnerability of breast cancer cells to PEMF exposure was corroborated in human tumor biopsy samples. Stable overexpression of TRPC1 enhanced the vulnerability of MCF-7 cells to both DOX and PEMF exposure and promoted proliferation, whereas TRPC1 genetic silencing reduced sensitivity to both DOX and PEMF treatments and mitigated proliferation. Chronic exposure to DOX depressed TRPC1 expression, proliferation, and responses to both PEMF exposure and DOX in a manner that was reversible upon removal of DOX. TRPC1 channel overexpression and silencing positively correlated with markers of epithelial-mesenchymal transition (EMT), including SLUG, SNAIL, VIMENTIN, and E-CADHERIN, indicating increased and decreased EMT, respectively. Finally, PEMF exposure was shown to attenuate the invasiveness of MCF-7 cells in correlation with TRPC1 expression. We thus demonstrate that the expression levels of TRPC1 consistently predicted breast cancer sensitivity to DOX and PEMF interventions and positively correlated to EMT status, providing an initial rationale for the use of PEMF-based therapies as an adjuvant to DOX chemotherapy for the treatment of breast cancers characterized by elevated TRPC1 expression levels.

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Section: Introductionmentioning

confidence: 99%

Modulated TRPC1 Expression Predicts Sensitivity of Breast Cancer to Doxorubicin and Magnetic Field Therapy: Segue Towards a Precision Medicine Approach

et al. 2022

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“…Previous studies have shown that strong oxidative stress, including exposure to hepatitis virus, chronic inflammation, and DNA damage, is associated with the progression of HCC [ 31 , 48 , 49 ]. Tsukiyama-Kohara et al reported that gene expression of hepatitis C virus suppresses p53 activity which, in turn, causes apoptotic resistance to oxidative stress [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Synthetic Tryptanthrin Derivatives Induce Cell Cycle Arrest and Apoptosis via Akt and MAPKs in Human Hepatocellular Carcinoma Cells

et al. 2021

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Trytanthrin, found in Ban-Lan-Gen, is a natural product containing an indoloquinazoline moiety and has been shown to possess anti-inflammatory and anti-viral activities. Chronic inflammation and hepatitis B are known to be associated with the progression of hepatocellular carcinoma (HCC). In this study, a series of tryptanthrin derivatives were synthesized to generate potent anti-tumor agents against HCC. This effort yielded two compounds, A1 and A6, that exhibited multi-fold higher cytotoxicity in HCC cells than the parent compound. Flow cytometric analysis demonstrated that A1 and A6 caused S-phase arrest and downregulated the expression of cyclin A1, B1, CDK2, and p-CDC2. In addition to inducing caspase-dependent apoptosis, A1 and A6 exhibited similar regulation of the phosphorylation or expression of multiple signaling targets, including Akt, NF-κB, and mitogen-activated protein kinases. The anti-tumor activities of A1 and A6 were also attributable to the generation of reactive oxygen species, accompanied by an increase in p-p53 levels. Therefore, A1 and A6 have potential clinical applications since they target diverse aspects of cancer cell growth in HCC.

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“…[ 148 ] Many pieces of research indicate that H 2 O 2 can upregulate cell division and proliferation gene transcription, facilitate cancer cells to infiltrate normal tissues, and enhance the viability of cancer cells. [ 149 ] Therefore, cancer cells are more sensitive than normal tissues and do not bear either excessively increased or decreased H 2 O 2 levels to induce dead tumors. Chang et al fabricated the hollow‐structured Cu 2 MoS 4 en‐srNP bioreactor for synergetic CDT, PDT, immunotherapy, and starvation therapy of tumors.…”

Section: Endo‐stimuli‐responsive Nanoparticles (En‐srnps) For Control...mentioning

confidence: 99%

Stimuli‐Responsive Nanoparticles for Controlled Drug Delivery in Synergistic Cancer Immunotherapy

Zhang

Lin

Lin³

et al. 2021

Advanced Science

137

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Cancer immunotherapy has achieved promising clinical progress over the recent years for its potential to treat metastatic tumors and inhibit their recurrences effectively. However, low patient response rates and dose-limiting toxicity remain as major dilemmas for immunotherapy. Stimuli-responsive nanoparticles (srNPs) combined with immunotherapy offer the possibility to amplify anti-tumor immune responses, where the weak acidity, high concentration of glutathione, overexpressions of enzymes, and reactive oxygen species, and external stimuli in tumors act as triggers for controlled drug release. This review highlights the design of srNPs based on tumor microenvironment and/or external stimuli to combine with different anti-tumor drugs, especially the immunoregulatory agents, which eventually realize synergistic immunotherapy of malignant primary or metastatic tumors and acquire a long-term immune memory to prevent tumor recurrence. The authors hope that this review can provide theoretical guidance for the construction and clinical transformation of smart srNPs for controlled drug delivery in synergistic cancer immunotherapy.

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Reactive oxygen species (ROS): Critical roles in breast tumor microenvironment

Cited by 52 publications

References 118 publications

Modulated TRPC1 Expression Predicts Sensitivity of Breast Cancer to Doxorubicin and Magnetic Field Therapy: Segue Towards a Precision Medicine Approach

Modulated TRPC1 Expression Predicts Sensitivity of Breast Cancer to Doxorubicin and Magnetic Field Therapy: Segue Towards a Precision Medicine Approach

Synthetic Tryptanthrin Derivatives Induce Cell Cycle Arrest and Apoptosis via Akt and MAPKs in Human Hepatocellular Carcinoma Cells

Stimuli‐Responsive Nanoparticles for Controlled Drug Delivery in Synergistic Cancer Immunotherapy

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