H2O2-Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways
Document Type
Article
Abstract
Mn(III) ortho-N-alkyl- and N-alkoxyalkyl porphyrins (MnPs) were initially developed as superoxide dismutase (SOD) mimics. These compounds were later shown to react with numerous reactive species (such as ONOO-, H2O2, H2S, CO3•-, ascorbate, and GSH). Moreover, the ability of MnPs to oxidatively modify activities of numerous proteins has emerged as their major mechanism of action both in normal and in cancer cells. Among those proteins are transcription factors (NF-κB and Nrf2), mitogen-activated protein kinases, MAPKs, antiapoptotic bcl-2, and endogenous antioxidative defenses. The lead Mn porphyrins, namely, MnTE-2-PyP5+ (BMX-010, AEOL10113), MnTnBuOE-2-PyP5+ (BMX-001), and MnTnHex-2-PyP5+, were tested in numerous injuries of normal tissue and cellular and animal cancer models. The wealth of the data led to the progression of MnTnBuOE-2-PyP5+ into fourPhase II clinical trials on glioma, head and neck cancer, anal cancer, and multiple brain metastases, while MnTE-2-PyP5+ is in Phase II clinical trial on atopic dermatitis and itch.
Publication Date
1-1-2021
Publication Title
Oxidative Medicine and Cellular Longevity
ISSN
19420900
E-ISSN
19420994
Volume
2021
PubMed ID
33815656
Digital Object Identifier (DOI)
10.1155/2021/6653790
Recommended Citation
Batinic-Haberle, Ines; Tovmasyan, Artak; Huang, Zhiqing; Duan, Weina; Du, Li; Siamakpour-Reihani, Sharareh; Cao, Zhipeng; Sheng, Huaxin; Spasojevic, Ivan; and Alvarez Secord, Angeles, "H2O2-Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways" (2021). Translational Neuroscience. 1268.
https://scholar.barrowneuro.org/neurobiology/1268