The interplay of oncogenic signaling, oxidative stress and ferroptosis in cancer

Abstract

Oncogene-induced hyper-proliferation in cancer cells is accompanied by the onset of different stresses, including DNA-replication stress, metabolic stress and oxidative stress. Excessive accumulation of reactive oxygen species (ROS) plays a pivotal and contradictory role in tumor progression. ROS dictates a multitude of cell signaling pathways to facilitate the malignant transformation of tumor cells. In the meantime, oxidative burden in tumor cells mandates reinforcing antioxidant capacity to mitigate detrimental damages. The addiction to oxidative stress and increased iron demands in cancer cells also impinges on the sensitivity of ferroptosis. Targeting redox homeostasis and ferroptosis to overcome drug resistance in cancer treatment has become an attractive research topic. However, the roles of oncogenic signaling in redox regulation and ferroptosis have not been comprehensively discussed. In this review, we summarize current knowledge regarding the interplay between redox regulation and ferroptosis in the context of cancer biology. We emphasize the implication of oncogenic signaling in redox homeostasis and ferroptosis regulation. We also provide an overview of strategies targeting oxidative stress and ferroptosis in cancer treatment.

Antioxidant Activity and Inhibition of Liver Cancer Cells’ Growth of Extracts from 14 Marine Macroalgae Species of the Mediterranean Sea

“…Since oxidative stress has been shown to be a causative factor for cancer [ 72 ], macroalgae extracts’ scavenging abilities against four different free radicals (i.e., DPPH, ABTS •+ , • OH, and O 2 • − ) were determined. The IC 50 values of all assays are shown in Table 2 .…”

“…On the contrary, • OH and O 2 •− radicals are formed naturally in the human organism [ 80 ]. The overproduction of O 2 •− within cells results in reactions with biological macromolecules, causing damage to cellular components and dysfunction of cell metabolism [ 72 ]. Moreover, intracellular superoxide dismutase (SOD) can catalyze O 2 •− to hydrogen peroxide (H 2 O 2 ) reacting through the Fenton reaction with Fe 2+ , leading to formation of • OH that may cause DNA damage and cancer [ 72 ].…”

“…The overproduction of O 2 •− within cells results in reactions with biological macromolecules, causing damage to cellular components and dysfunction of cell metabolism [ 72 ]. Moreover, intracellular superoxide dismutase (SOD) can catalyze O 2 •− to hydrogen peroxide (H 2 O 2 ) reacting through the Fenton reaction with Fe 2+ , leading to formation of • OH that may cause DNA damage and cancer [ 72 ]. Thus, the identification of compounds being able to scavenge both • OH and O 2 •− radicals is of great importance for cancer prevention.…”

Insight into Iron, Oxidative Stress and Ferroptosis: Therapy Targets for Approaching Anticancer Strategies

“…Ferroptotic machinery can be finely regulated by both oncosuppressors and oncogenes, which act as suppressors or promoters of ferroptosis, respectively [ 91 , 157 ]. The dual role of ferroptosis in cancer is widely reported in the literature.…”

Cancer Bioenergetics and Tumor Microenvironments—Enhancing Chemotherapeutics and Targeting Resistant Niches through Nanosystems

“…OXPHOS is a preferred energy pathway in CSC, which exhibit higher oxygen consumption rates, ROS production, and a substantial increase in mitochondrial mechanics compared to non-stem cancer cells [145]. Further, mitochondrial ROS also promotes Kirsten rat sarcoma viral oncogene homolog (KRAS)-induced anchorage-independent cancerous growth [146,147].…”