Crosstalk Between ROS and Autophagy in Tumorigenesis: Understanding the Multifaceted Paradox

Hasan, Adria; Rizvi, Suroor Fatima; Parveen, Sana; Pathak, Neelam; Nazir, Aamir; Mir, Snober S.

doi:10.3389/fonc.2022.852424

Cited by 34 publications

(23 citation statements)

References 295 publications

(254 reference statements)

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“…Autophagy can be perceived from a dual perspective. Its inhibition was reported to promote carcinogenesis in cells with a genome subjected to accumulated reactive oxygen species [ 54 ]. On the other hand, autophagy induction was shown to provide tumor cell survival in unfavorable conditions, such as insufficient nutrient supply, hypoxia, acidosis, or chemotherapeutic agent exposition [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

Biological Activity of Oleanolic Acid Derivatives HIMOXOL and Br-HIMOLID in Breast Cancer Cells Is Mediated by ER and EGFR

Lisiak

Dzikowska

Wisniewska

et al. 2023

IJMS

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Breast cancer is one of the most frequently observed malignancies worldwide and represents a heterogeneous group of cancers. For this reason, it is crucial to properly diagnose every single case so a specific and efficient therapy can be adjusted. One of the most critical diagnostic parameters evaluated in cancer tissue is the status of the estrogen receptor (ER) and epidermal growth factor receptor (EGFR). Interestingly, the expression of the indicated receptors may be used in a personalized therapy approach. Importantly, the promising role of phytochemicals in the modulation of pathways controlled by ER and EGFR was also demonstrated in several types of cancer. One such biologically active compound is oleanolic acid, but due to poor water solubility and cell membrane permeability that limits its use, alternative derivative compounds were developed. These are HIMOXOL and Br-HIMOLID, which were demonstrated to be capable of inducing apoptosis and autophagy or diminishing the migratory and invasive potential of breast cancer cells in vitro. In our study, we revealed that proliferation, cell cycle, apoptosis, autophagy, and also the migratory potential of HIMOXOL and Br-HIMOLID in breast cancer cells are mediated by ER (MCF7) and EGFR (MDA-MB-231) receptors. These observations make the studied compounds interesting in the context of anticancer strategies.

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Section: Discussionmentioning

confidence: 99%

Biological Activity of Oleanolic Acid Derivatives HIMOXOL and Br-HIMOLID in Breast Cancer Cells Is Mediated by ER and EGFR

Lisiak

Dzikowska

Wisniewska

et al. 2023

IJMS

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show abstract

“…In cancer cells, autophagy has been reported to play a dual role, initially acting as a tumor suppressor process, and as promoting tumor progression during the advanced stages; an intricate link between autophagy and oxidative stress has also been reported [ 84 ]. Moreover, autophagy is strictly interconnected with apoptosis and different cross-talk between them have been highlighted depending on the type of cells [ 85 ].…”

Section: Discussionmentioning

confidence: 99%

β-Caryophyllene Counteracts Chemoresistance Induced by Cigarette Smoke in Triple-Negative Breast Cancer MDA-MB-468 Cells

et al. 2022

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Exposure to cigarette smoke (CS) has been associated with an increased risk of fatal breast cancers and recurrence, along with chemoresistance and chemotherapy impairment. This strengthens the interest in chemopreventive agents to be exploited both in healthy and oncological subjects to prevent or repair CS damage. In the present study, we evaluated the chemopreventive properties of the natural sesquiterpene β-caryophyllene towards the damage induced by cigarette smoke condensate (CSC) in triple negative breast cancer MDA-MB-468 cells. Particularly, we assessed the ability of the sesquiterpene to interfere with the mechanisms exploited by CSC to promote cell survival and chemoresistance, including genomic instability, cell cycle progress, autophagy/apoptosis, cell migration and related pathways. β-Caryophyllene was found to be able to increase the CSC-induced death of MDA-MB-468 cells, likely triggering oxidative stress, cell cycle arrest and apoptosis; moreover, it hindered cell recovery, autophagy activation and cell migration; at last, a marked inhibition of the signal transducer and activator of transcription 3 (STAT3) activation was highlighted: this could represent a key mechanism of the chemoprevention by β-caryophyllene. Although further studies are required to confirm the in vivo efficacy of β-caryophyllene, the present results suggest a novel strategy to reduce the harmful effect of smoke in cancer patients and to improve the survival expectations in breast cancer women.

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“…WPS exposure also induces hypoxia [ 56 ]. Reactive oxygen species (ROS) could also be generated because of an increase in apoptotic cell death [ 57 ], which could generate a positive feed-back to further activate autophagy pathways [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Genomic Analysis of Waterpipe Smoke-Induced Lung Tumor Autophagy and Plasticity

Zaarour

Sharda

Azakir

et al. 2022

IJMS

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The role of autophagy in lung cancer cells exposed to waterpipe smoke (WPS) is not known. Because of the important role of autophagy in tumor resistance and progression, we investigated its relationship with WP smoking. We first showed that WPS activated autophagy, as reflected by LC3 processing, in lung cancer cell lines. The autophagy response in smokers with lung adenocarcinoma, as compared to non-smokers with lung adenocarcinoma, was investigated further using the TCGA lung adenocarcinoma bulk RNA-seq dataset with the available patient metadata on smoking status. The results, based on a machine learning classification model using Random Forest, indicate that smokers have an increase in autophagy-activating genes. Comparative analysis of lung adenocarcinoma molecular signatures in affected patients with a long-term active exposure to smoke compared to non-smoker patients indicates a higher tumor mutational burden, a higher CD8+ T-cell level and a lower dysfunction level in smokers. While the expression of the checkpoint genes tested—PD-1, PD-L1, PD-L2 and CTLA-4—remains unchanged between smokers and non-smokers, B7-1, B7-2, IDO1 and CD200R1 were found to be higher in non-smokers than smokers. Because multiple factors in the tumor microenvironment dictate the success of immunotherapy, in addition to the expression of immune checkpoint genes, our analysis explains why patients who are smokers with lung adenocarcinoma respond better to immunotherapy, even though there are no relative differences in immune checkpoint genes in the two groups. Therefore, targeting autophagy in lung adenocarcinoma patients, in combination with checkpoint inhibitor-targeted therapies or chemotherapy, should be considered in smoker patients with lung adenocarcinoma.

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Crosstalk Between ROS and Autophagy in Tumorigenesis: Understanding the Multifaceted Paradox

Cited by 34 publications

References 295 publications

Biological Activity of Oleanolic Acid Derivatives HIMOXOL and Br-HIMOLID in Breast Cancer Cells Is Mediated by ER and EGFR

Biological Activity of Oleanolic Acid Derivatives HIMOXOL and Br-HIMOLID in Breast Cancer Cells Is Mediated by ER and EGFR

β-Caryophyllene Counteracts Chemoresistance Induced by Cigarette Smoke in Triple-Negative Breast Cancer MDA-MB-468 Cells

Genomic Analysis of Waterpipe Smoke-Induced Lung Tumor Autophagy and Plasticity

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