Abstract
Platinum-based antitumor drugs play important roles in the clinical treatment of various tumors. Nevertheless, some deficiencies such as poor targeting ability, low bioavailability, in vivo deactivation, drug resistance, and side effects undermine the efficacy of these drugs. Mitochondria are important organelles which regulate the energy metabolism, physiological function, life span, and survival of the cells. Regulating or interfering with mitochondrial metabolism is of great significance in the prevention or treatment of cancers. Thus, a series of mitochondrion-targeted platinum complexes were prepared by modifying triphenylphosphine (TPP+) through chemical modifications, which endow traditional platinum drugs with new properties and mechanisms through interfering with mitochondrial DNA (mtDNA), mitochondrial membrane potential (MMP), mitochondrial morphology, mitochondrial bioenergetics, or production of reactive oxygen species (ROS), thereby opening a new path for the clinical application of platinum drugs. Here we introduce the synthesis of some TPP+-modified platinum (II, IV) complexes in details and the detection method of the activity parameters related to the mitochondrial functions.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Johnstone TC, Suntharalingam K, Lippard SJ (2016) The next generation of platinum drugs: targeted Pt(II) agents, nanoparticle delivery, and Pt(IV) prodrugs. Chem Rev 116:3436–3486
Deo KM, Ang DL, McGhie B et al (2018) Platinum coordination compounds with potent anticancer activity. Coord Chem Rev 375:148–163
Wang XY, Guo ZJ (2013) Targeting and delivery of platinum-based anticancer drugs. Chem Soc Rev 42:202–224
Wang XH, Wang XY, Guo ZJ (2019) Stimuli-responsive therapeutic metallodrugs. Chem Rev 119:1138–1192
Zhang W, Zhang SL, Hu XH et al (2015) Targeting tumor metabolism for cancer treatment: is pyruvate dehydrogenase kinases (PDKs) a viable anticancer target? Int J Biol Sci 11:1390–1400
Chipuk JE, Bouchier-Hayes L, Green DR (2016) Mitochondrial outer membrane permeabilization during apoptosis: the innocent bystander scenario. Cell Death Differ 13:1396–1402
Santo-Domingo J, Demaurex N (2010) Calcium uptake mechanisms of mitochondria. Biochim Biophys Acta (BBA) Bioenerg 1797:907–912
Youle RJ, Bliek AM (2012) Mitochondrial fission, fusion, and stress. Science 337:1062–1065
Martinou JC, Youle RJ (2011) Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell 21:92–101
Souers AJ, Leverson JD, Boghaert ER et al (2013) ABT-199, a potent and selective Bcl-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med 19:202–208
Fulda S, Galluzzi L, Kroemer G (2010) Targeting mitochondria for cancer therapy. Nature 9:447–464
Chen LB (1988) Mitochondrial membrane potential in living cells. Annu Rev Cell Biol 4:155–181
Weinberg SE, Chandel NS (2015) Targeting mitochondria metabolism for cancer therapy. Nat Chem Biol 11:9–15
Zielonka J, Joseph J, Sikora A et al (2017) Mitochondria-targeted triphenylphosphonium-based compounds: syntheses, mechanisms of action, and therapeutic and diagnostic applications. Chem Rev 117:10043–10120
Guo Y, Guo ZJ, Wang XY et al (2019) Enhancing Cytotoxicity of a monofunctional platinum complex via a dual-DNA-damage approach. Inorg Chem 58:13150–13160
Wang K, Wang XY, Guo ZJ et al (2019) Restraining cancer cells by dual metabolic inhibition with a mitochondrion-targeted platinum(II) complex. Angew Chem Int Ed 58:4638–4643
Zhu ZZ, Guo ZJ, Wang XY et al (2019) Mitochondrion-targeted platinum complexes suppressing lung cancer through multiple pathways involving energy metabolism. Chem Sci 10:3089–3095
Jin SX, Guo ZJ, Wang XY et al (2018) Impact of mitochondrion-targeting group on the reactivity and cytostatic pathway of platinum(IV) complexes. Inorg Chem 57:11135–11145
Zhang J, Nuebel E, Koehler CM et al (2012) Measuring energy metabolism in cultured cells, including human pluripotent stem cells and differentiated cells. Nat Protoc 7:1068–1085
Acknowledgments
We acknowledge the National Natural Science Foundation of China (Grants 31570809, 21877059).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Jin, S., Wang, X. (2021). Assessing Impact of Platinum Complexes on Mitochondrial Functions. In: Weissig, V., Edeas, M. (eds) Mitochondrial Medicine . Methods in Molecular Biology, vol 2276. Springer, New York, NY. https://doi.org/10.1007/978-1-0716-1266-8_30
Download citation
DOI: https://doi.org/10.1007/978-1-0716-1266-8_30
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-0716-1265-1
Online ISBN: 978-1-0716-1266-8
eBook Packages: Springer Protocols