Pathological and Pharmacological Roles of Mitochondrial Reactive Oxygen Species in Malignant Neoplasms: Therapies Involving Chemical Compounds, Natural Products, and Photosensitizers

Abstract

Oxidative stress plays an important role in cellular processes. Consequently, oxidative stress also affects etiology, progression, and response to therapeutics in various pathological conditions including malignant tumors. Oxidative stress and associated outcomes are often brought about by excessive generation of reactive oxygen species (ROS). Accumulation of ROS occurs due to dysregulation of homeostasis in an otherwise strictly controlled physiological condition. In fact, intracellular ROS levels are closely associated with the pathological status and outcome of numerous diseases. Notably, mitochondria are recognized as the critical regulator and primary source of ROS. Damage to mitochondria increases mitochondrial ROS (mROS) production, which leads to an increased level of total intracellular ROS. However, intracellular ROS level may not always reflect mROS levels, as ROS is not only produced by mitochondria but also by other organelles such as endoplasmic reticulum and peroxisomes. Thus, an evaluation of mROS would help us to recognize the biological and pathological characteristics and predictive markers of malignant tumors and develop efficient treatment strategies. In this review, we describe the pathological significance of mROS in malignant neoplasms. In particular, we show the association of mROS-related signaling in the molecular mechanisms of chemically synthesized and natural chemotherapeutic agents and photodynamic therapy.

Modulation of redox-sensitive transcription factors with polyphenols as pathogenetically grounded approach in therapy of systemic inflammatory response

“…Replacement of the carbonyl group of the lactone function of the classic coumarin framework with cyano-(4-pyridine/pyrimidine)-methylene parts allows coumarins to interact with visible light and affect cell mitochondria, increasing the production of reactive oxygen species from the mitochondrial electron transport chain and leading to tumour cell apoptosis [ 134 ]. Tannic acids can induce apoptosis of tumour cells by regulating mitochondrial production of reactive oxygen species [ 135 , 136 ].…”

Pathological Significance of Macrophages in Erectile Dysfunction Including Peyronie’s Disease

“…In addition, lifestyle modifications, including physical activity, are known to be useful in improving erectile function and the efficacy of PDE5 inhibitors [ 56 , 103 ]. Moreover, numerous nutraceuticals and natural products have been reported to have beneficial effects and therapeutic benefits for various disorders and diseases [ 104 , 105 , 106 ]. In fact, many types of botanical medicines and natural products are reported to be useful for the prevention and treatment of ED [ 107 , 108 ].…”

Modulation by Phosphonium Ions of the Activity of Mitotropic Agents Based on the Chemiluminescence of Luminols

“…Up to 90% of cells' energy unit ATP [4] and cytotoxic ROS [5] are generated in mitochondria. As a result, mitochondrial malfunction, causing ROS overproduction, is connected to pathogenesis, such as neurodegenerative diseases, cancer, and diabetes [6][7][8].…”