Utilizing Iron for Targeted Lipid Peroxidation as Anticancer Option of Integrative Biomedicine: A Short Review of Nanosystems Containing Iron

Abstract

Traditional concepts of life sciences consider oxidative stress as a fundamental process of aging and various diseases including cancer, whereas traditional medicine recommends dietary intake of iron to support physiological functions of the organism. However, due to its strong pro-oxidative capacity, if not controlled well, iron can trigger harmful oxidative stress manifested eventually by toxic chain reactions of lipid peroxidation. Such effects of iron are considered to be major disadvantages of uncontrolled iron usage, although ferroptosis seems to be an important defense mechanism attenuating cancer development. Therefore, a variety of iron-containing nanoparticles were developed for experimental radio-, chemo-, and photodynamic as well as magnetic dynamic nanosystems that alter redox homeostasis in cancer cells. Moreover, studies carried over recent decades have revealed that even the end products of lipid peroxidation, represented by 4-hydroxynonenal (4-HNE), could have desirable effects even acting as kinds of selective anticancer substances produced by non-malignant cells for defense again invading cancer. Therefore, advanced nanotechnologies should be developed for using iron to trigger targeted lipid peroxidation as an anticancer option of integrative biomedicine.

The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

“…Transition metals, such as iron, can promote ROS and support tumorigenesis [19,20]. O 2 •− and H 2 O 2 are accessible to iron via the Fenton reaction, converting them to • OH, and can contribute to the initiation of ferroptosis [21], which is also considered in anticancer approaches as a potential target for oncotherapy [22]. On the other hand, ROS can also damage DNA, causing strand breaks or oxidative DNA lesions.…”

Targeting Lipid Peroxidation for Cancer Treatment

“…Some recent advances have been made regarding the synthesis of NPs loaded with metals, mainly with iron, which can facilitate lipid peroxidation in cancer cells [234,238,239]. As previously indicated, iron overload produces an increase in random peroxidation products that is entirely unspecific and could lead to harmful oxidative stress in non-cancer cells.…”

“…Some recent advances have been made regarding the synthesis of NPs loaded with metals, mainly with iron, which can facilitate lipid peroxidation in cancer cells [234,238,239]. As previously indicated, iron overload produces an increase in random peroxidation products that is entirely DHODH 14 [229] 2-(4-(2,6-difluorophenoxy)-3isopropoxy-5-methy l-1H-pyrazol-1-yl) -5-ethylpyrimidine (BDBM50070908) [230] 0.02 (Jurkat cells) Human lymphocytes [231] Molecules 2020, 25 14 [229] 2-(4-(2,6-difluorophenoxy)-3-isopropoxy-5-methyl-1Hpyrazol-1-yl)-5ethylpyrimidine (BDBM50070908) [230] 0.02 (Jurkat cells) Human lymphocytes [231] Kinetic parameters were obtained from BRENDA enzyme database [89].…”

α‐Lipoic acid alleviates ferroptosis in the MPP+‐induced PC12 cells via activating the PI3K/Akt/Nrf2 pathway

“…α‐LA serves as a critical part in preventing neuronal loss and ferroptosis (Y. H. Zhang, Wang, et al, 2018). Ferroptosis is a kind of cell control death related to the accumulation of lipid‐related reactive oxygen species (ROS), accompanied by increased iron concentration and malondialdehyde (MDA) level (Huang et al, 2020), and 4‐hydroxynonenal (4‐HNE) is a final product of lipid peroxidation (Jaganjac et al, 2020). Ferroptosis is an iron‐dependent form of regulated cell death and has been proven to be related to various neurodegenerative diseases (Guiney et al, 2017; Weiland et al, 2019; Zhou et al, 2020).…”