Multifactorial Distress, the Warburg Effect, and Respiratory and pH Imbalance in Cancer Development

Abstract

Oncogenes are thought to play an important role in aberrant regulation of growth factors, which is believed to be an initiation event of carcinogenesis. However, recent genetic and pharmacological studies have shown that the Warburg effect (WE) is needed for tumour growth. It refers to extensively studied aerobic glycolysis over the past decade, although its impact on cancer remains unclear. Meanwhile, a large body of evidence has indicated that oxidative stress (OS) is connected with the occurrence and progression of various forms of cancer. Psychosocial factors (PSF), such as chronic depression, sadness, stressful life experiences, stress-prone personality, and emotional distress or poor quality of life affect the immune system and contribute to cancer outcomes. Here, we examine the relationship between WE, OS, PSF, metal ions, other carcinogens, and the development of different cancers from the viewpoint of physiological and biochemical mechanisms.

Oxidative Stress and ROS Link Diabetes and Cancer

“…If there is a single "switch", ROS must be considered the prime candidate. Indeed, while recognizing that cancer initiation may be due to multifactorial stressors, evidence suggests a close relationship between oxidative stress and carcinogenesis [185,186]. In addition, ROS not only leads to redox imbalance but functions as signaling molecules that activate signal transduction pathways that promote many aspects of tumor development and progression, expressed in the cancer phenotype.…”

Toxicity Tolerance in the Carcinogenesis of Environmental Cadmium

“…The generation of cancer cells simply by exposure of various cell types to low-level Cd over a long period of time (Table 4) provides further evidence that Cd is a mutitissue carcinogen as it has been observed in both Cd-exposed humans (Table 2) and Cdexposed mice (Section 4.2). The Cd-transformed cells (transformants) have been of utility to investigate the molecular fingerprints that can be linked to cellular adaptive responses, enabling the transformant to resist cell death, and acquired cancer cell phenotypes such as metabolic reprogramming to glycolysis dominance, known as the Warburg effect [154][155][156]. The notable impact of Cd on cellular gene expression profiles has been studied extensively using various types of cancer cells, including MCF-7 breast cancer cells, A549 lung cancer cells, and HepG2 hepatocellular carcinoma cells [157][158][159] Among the susceptible cells, the UROtsa urothelial cell line is noteworthy because of the limited human cell models of human urinary bladder cancer, which has a high recurrence rate.…”