Oxaliplatin

Oxaliplatin, a diaminocyclohexane-containing platinum, exhibits potent cytotoxicity^[1]. Oxaliplatin binds to DNA to form DNA adducts, which inhibit DNA replication and induce early and persistent DNA strand breaks, ultimately leading to cell death^[2]. Oxaliplatin has been widely used in tumor research to induce nucleolar stress and inhibit the growth of various tumor cells^[3].

In vitro, Oxaliplatin treatment for 24 hours significantly inhibited the viability of LoVo, SW620 and HT-29 cells, with IC₅₀ values of 0.3μM, 0.4μM and 0.9μM, respectively^[4]. Treatment with 10μM Oxaliplatin for 24 hours induced autophagy and endoplasmic reticulum stress in Caco-2 cells, and increased the level of reactive oxygen species (ROS) within the cells^[5]. Treatment with 30μM Oxaliplatin for 72 hours triggered G2/M phase cell cycle arrest in A549 cells^[6].

In vivo, Oxaliplatin administration via intraperitoneal injection at a dose of 2.5mg/kg, four times weekly for 3 weeks induced hematotoxicity and splenomegaly in mice^[7]. Intraperitoneal injection of Oxaliplatin at a dose of 8mg/kg/day for 3 consecutive days evoked acute liver injury, aggravated intrahepatic oxidative stress, and promoted hepatic fibrosis in mice with non-alcoholic fatty liver disease (NAFLD)^[8].

References:

[1] Graham J, Muhsin M, Kirkpatrick P. Oxaliplatin[J]. Nature reviews Drug discovery, 2004, 3(1): 11-12.

[2] Raymond E, Faivre S, Chaney S, et al. Cellular and molecular pharmacology of oxaliplatin[J]. Molecular cancer therapeutics, 2002, 1(3): 227-235.

[3] O'Dowd P D, Sutcliffe D F, Griffith D M. Oxaliplatin and its derivatives–An overview[J]. Coordination Chemistry Reviews, 2023, 497: 215439.

[4] Arnould S, Hennebelle I, Canal P, et al. Cellular determinants of oxaliplatin sensitivity in colon cancer cell lines[J]. European journal of cancer, 2003, 39(1): 112-119.

[5] Shi Y, Tang B, Yu P W, et al. Autophagy protects against oxaliplatin-induced cell death via ER stress and ROS in Caco-2 cells[J]. PloS one, 2012, 7(11): e51076.

[6] William‐Faltaos S, Rouillard D, Lechat P, et al. Cell cycle arrest by oxaliplatin on cancer cells[J]. Fundamental & clinical pharmacology, 2007, 21(2): 165-172.

[7] Lees J G, White D, Keating B A, et al. Oxaliplatin-induced haematological toxicity and splenomegaly in mice[J]. Plos one, 2020, 15(9): e0238164.

[8] Lu Y, Lin Y, Huang X, et al. Oxaliplatin aggravates hepatic oxidative stress, inflammation and fibrosis in a non-alcoholic fatty liver disease mouse model[J]. International Journal of Molecular Medicine, 2019, 43(6): 2398-2408.