Role of Reactive Oxygen Species in Cancer Progression: Molecular Mechanisms and Recent Advancements

Abstract

Reactive oxygen species (ROS) play a pivotal role in biological processes and continuous ROS production in normal cells is controlled by the appropriate regulation between the silver lining of low and high ROS concentration mediated effects. Interestingly, ROS also dynamically influences the tumor microenvironment and is known to initiate cancer angiogenesis, metastasis, and survival at different concentrations. At moderate concentration, ROS activates the cancer cell survival signaling cascade involving mitogen-activated protein kinase/extracellular signal-regulated protein kinases 1/2 (MAPK/ERK1/2), p38, c-Jun N-terminal kinase (JNK), and phosphoinositide-3-kinase/ protein kinase B (PI3K/Akt), which in turn activate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), matrix metalloproteinases (MMPs), and vascular endothelial growth factor (VEGF). At high concentrations, ROS can cause cancer cell apoptosis. Hence, it critically depends upon the ROS levels, to either augment tumorigenesis or lead to apoptosis. The major issue is targeting the dual actions of ROS effectively with respect to the concentration bias, which needs to be monitored carefully to impede tumor angiogenesis and metastasis for ROS to serve as potential therapeutic targets exogenously/endogenously. Overall, additional research is required to comprehend the potential of ROS as an effective anti-tumor modality and therapeutic target for treating malignancies.

Evaluation of the Cytotoxic Activity of the Usnea barbata (L.) F. H. Wigg Dry Extract

“…Thus, in cancer pathology, the reactive oxygen species (ROS) have dual role, confirmed by many studies: first, ROS are cytotoxic, having an important contribution in the etiology and progression of cancer [3]. At the same time, many antitumor agents can destroy the cancer cells through intense oxidative stress, generating ROS production in high quantities [4]. Increasing ROS levels through redox modulation could in the future be an effective strategy for the selective destruction of cancer cells (not normal cells) [5]; this method is called "oxidative therapy" [6], and it was developed by inducing cytotoxic oxidation as a stress factor in cancer cells in the treatment of cancer [7].One of the most invasive malignancies is the oral squamous cell carcinoma (OSCC), which is the most common cancer of oral cavity; it can affect any part of the oral cavity including lips, tongue, gums, buccal epithelium, and salivary glands [8].…”

Cytotoxic activity of dimeric acridone alkaloids derived from Citrus plants towards human leukaemia HL-60 cells

“…Several studies have illustrated that anticancer agents exert their anticancer activity by generating ROS. [26,27] Targeting of ROS-mediated oxidative stress has been found to be a useful strategy for developing chemotherapeutics in the treatment of acute myeloid leukaemia cells. [28][29][30] Natural products isolated from living organism sources not only trigger apoptotic cell death but also reduce resistance to chemotherapies in leukaemia cells.…”

2α-Hydroxyeudesma-4,11(13)-Dien-8β,12-Olide Isolated from Inula britannica Induces Apoptosis in Diffuse Large B-cell Lymphoma Cells

“…To prove ROS-mediated apoptosis induced in OCI-LY3 lymphoma cells, we performed an apoptosis assay using PI/annexin V-APC for FACS analysis after 24 and 48 h using the OCI-LY3 cell line (Supplementary Figure S3). The apoptosis analysis results showed that HEDO (10 µM) treatment for 24 and 48 h also markedly induced the percentages of early and late apoptotic cells in a time-dependent manner, which reached a maximum after 72 h. Many types of cancer cells exhibit increased levels of ROS, and ROS production has been proven to be associated with apoptosis caused by anticancer agents [55]. Accordingly, an accumulation of ROS corresponds to apoptosis, suggesting its importance in the anticancer activity of HEDO.…”