Altered Retrograde Signaling Patterns in Breast Cancer Cells Cybrids with H and J Mitochondrial DNA Haplogroups

Chang, Steven S.; Singh, Lata; Thaker, Kunal; Abedi, Sina; Singh, Meharban; Patel, Tej; Chwa, Marilyn; Atilano, Shari R.; Udar, Nitin; Bota, Daniela; Kenney, M. Cristina

doi:10.3390/ijms23126687

Cited by 3 publications

(2 citation statements)

References 31 publications

(58 reference statements)

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“…Since mitochondria possess their DNA, BAK/BAX-mediated mitochondrial damage triggers the release of mitochondrial DNA (mtDNA). Consequently, the cGAS-STING-mediated cytoplasmic DNA sensing pathway identifies mtDNA and initiates apoptosis ( White et al, 2014 ; McArthur et al, 2018 ; Chang S. et al, 2022 ). Mitochondrial inner membrane permeabilisation enables the release of mtDNA into the cytoplasm and activates the cGAS-STING signalling pathway ( Riley et al, 2018 ).…”

Section: Mitochondrial Function and The Cgas-sting Pathway In Breast ...mentioning

confidence: 99%

Targeting the stimulator of interferon genes (STING) in breast cancer

et al. 2023

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Breast cancer has a high occurrence rate globally and its treatment has demonstrated clinical efficacy with the use of systemic chemotherapy and immune checkpoint blockade. Insufficient cytotoxic T lymphocyte infiltration and the accumulation of immunosuppressive cells within tumours are the primary factors responsible for the inadequate clinical effectiveness of breast cancer treatment. The stimulator of interferon genes (STING) represents a pivotal protein in the innate immune response. Upon activation, STING triggers the activation and enhancement of innate and adaptive immune functions, resulting in therapeutic benefits for malignant tumours. The STING signalling pathway in breast cancer is influenced by various factors such as deoxyribonucleic acid damage response, tumour immune microenvironment, and mitochondrial function. The use of STING agonists is gaining momentum in breast cancer research. This review provides a comprehensive overview of the cyclic guanosine monophosphate-adenosine monophosphate synthase-STING pathway, its agonists, and the latest findings related to their application in breast cancer.

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Section: Mitochondrial Function and The Cgas-sting Pathway In Breast ...mentioning

confidence: 99%

Targeting the stimulator of interferon genes (STING) in breast cancer

et al. 2023

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“…Transmitochondrial cybrids (cell lines with identical nuclei but mitochondria from different individuals) are one approach to elucidating the functional consequences of possessing mtDNA from healthy subjects versus subjects with diseases [ 17 , 18 ]. Furthermore, the cybrid model is excellent to characterize the molecular and biological responses of an individual’s mitochondria to specific exogenous treatment regimens [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Using Human ‘Personalized’ Cybrids to Identify Drugs/Agents That Can Regulate Chronic Lymphoblastic Leukemia Mitochondrial Dysfunction

Singh

Atilano

Chwa

et al. 2023

IJMS

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This study uses personalized chronic lymphoblastic leukemia (CLL) cybrid cells to test various drugs/agents designed to improve mitochondrial function and cell longevity. Age-matched control (NL) and CLL cybrids were created. The NL and CLL cybrids were treated with ibrutinib (Ibr-10 μM), mitochondrial-targeted nutraceuticals such as alpha lipoic acid (ALA-1 mM), amla (Aml-300 μg), melatonin (Mel-1 mM), resveratrol (Res-100 μM) alone, or a combination of ibrutinib with nutraceuticals (Ibr + ALA, Ibr + Aml, Ibr + Mel, or Ibr + Res) for 48 h. MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazoliumbromide), H2DCFDA(2′,7′ Dichlorodihydrofluorescein diacetate), and JC1 assays were used to measure the cellular metabolism, intracellular ROS levels, and mitochondrial membrane potential (∆ψm), respectively. The expression levels of genes associated with antioxidant enzymes (SOD2, GPX3, and NOX4), apoptosis (BAX and CASP3), and inflammation (IL6, IL-1β, TNFα, and TGFβ) were measured using quantitative real-time PCR (qRT-PCR). CLL cybrids treated with Ibr + ALA, Ibr + Aml, Ibr + Mel, and Ibr + Res had (a) reduced cell survivability, (b) increased ROS production, (c) increased ∆ψm levels, (d) decreased antioxidant gene expression levels, and (e) increased apoptotic and inflammatory genes in CLL cybrids when compared with ibrutinib-alone-treated CLL cybrids. Our findings show that the addition of nutraceuticals makes the CLL cybrids more pro-apoptotic with decreased cell survival compared with CLL cybrids exposed to ibrutinib alone.

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