Modulation of Cellular Redox Parameters for Improving Therapeutic Responses in Multiple Myeloma

Abstract

Raised oxidative stress and abnormal redox status are typical features of multiple myeloma cells, and the identification of the intimate mechanisms that regulate the relationships between neoplastic cells and redox homeostasis may reveal possible new anti-myeloma therapeutic targets to increase the effectiveness of anti-myeloma drugs synergistically or to eradicate drug-resistant clones while reducing toxicity toward normal cells. An alteration of the oxidative state is not only responsible for the onset of multiple myeloma and its progression, but it also appears essential for the therapeutic response and for developing any chemoresistance. Our review aimed to evaluate the literature’s current data on the effects of oxidative stress on the response to drugs generally employed in the therapy of multiple myeloma, such as proteasome inhibitors, immunomodulators, and autologous transplantation. In the second part of the review, we analyzed the possibility of using other substances, often of natural origin, to modulate the oxidative stress to interfere with the progression of myelomatous disease.

The role of pentraxin 3 and oxidative status in the prognosis of multiple myeloma

“…28 A change in oxidative status is not only responsible for the initiation and progression of MM but also considered crucial for achieving therapeutic responses and preventing the development of chemoresistance. 29 Numerous studies demonstrate that excessive ROS production inhibits the proliferation, viability, and transformation into various phenotypes of tumor cells. 30 Nevertheless, studies have also shown an increase in antioxidant parameters such as superoxide dismutase, catalase, glutathione peroxidase, and nitric oxide, as well as a decrease in oxidative stress parameters in MM patients post-treatment.…”

The Anti-Cancer Effect of Cinnamon Aqueous Extract: A Focus on Hematological Malignancies

“…Allegra and colleagues [ 33 ] studied the effects of rosemary in various types of cancer and put in evidence its action in augmenting antioxidant molecules, decreasing pro-inflammatory cytokines and preventing neo-vascularization, all functions crucial for the insurgence and progression of a tumor in general. In a work, the authors analyzed aqueous cinnamon extract and showed that its mechanisms of action are similar to those of rosemary; in particular, they collected experiences from different scientists and demonstrated that cinnamon extract has a role in hematological malignancies such as leukemia and lymphoma because it is capable of inhibiting the pathways and molecules involved in cellular proliferation: it ties to NF-KB and AP-1, determining a decrease in the correspondent RNA expression and translation and preventing the anti-apoptotic action of Bcl-2 [ 1 ]; furthermore, cinnamon extract modifies the function of PI3K/Akt/mTOR, dihydrofolate reductase and COX-2, with the consequences of blocking proliferation cell mechanisms and inflammation cascade signals [ 6 , 71 , 72 , 73 , 74 , 75 , 76 ] ( Figure 3 ). However, there are different limits which make us still far from using this compound in everyday practice.…”

Critical Role of Aquaporins in Cancer: Focus on Hematological Malignancies

“…Other molecular mechanisms have been recognized as essential moments of the effect exerted by AQPs on leukemic cells, such as their ability to modify the redox homeostasis. Reactive oxygen species (ROS) can work as regulators in cell signaling systems, and it is ascertained that an increase in intracellular ROS concentration causes cell proliferation, participating to tumor progression [ 91 , 92 , 93 ]. Amongst ROS, H 2 O 2 is considered the principal effector in redox signaling owing to its steadiness and capability of diffusion [ 94 ].…”