Elucidating role of reactive oxygen species (Ros) in cisplatin chemotherapy: a focus on molecular pathways and possible therapeutic strategies

Mirzaei, Sepideh and Hushmandi, Kiavash and Zabolian, Amirhossein and Saleki, Hossein and Torabi, Seyed Mohammad Reza and Ranjbar, Adnan and Seyedsaleh, Seyedhesam and Sharifzadeh, Seyed Omid and Khan, Haroon and Ashrafizadeh, Milad and Zarrabi, Ali and Ahn, Kwang Seok (2021) Elucidating role of reactive oxygen species (Ros) in cisplatin chemotherapy: a focus on molecular pathways and possible therapeutic strategies. Molecules, 26 (8). ISSN 1420-3049

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The failure of chemotherapy is a major challenge nowadays, and in order to ensure effective treatment of cancer patients, it is of great importance to reveal the molecular pathways and mechanisms involved in chemoresistance. Cisplatin (CP) is a platinum-containing drug with anti-tumor activity against different cancers in both pre-clinical and clinical studies. However, drug resistance has restricted its potential in the treatment of cancer patients. CP can promote levels of free radicals, particularly reactive oxygen species (ROS) to induce cell death. Due to the double-edged sword role of ROS in cancer as a pro-survival or pro-death mechanism, ROS can result in CP resistance. In the present review, association of ROS with CP sensitivity/resistance is discussed, and in particular, how molecular pathways, both upstream and downstream targets, can affect the response of cancer cells to CP chemotherapy. Furthermore, anti-tumor compounds, such as curcumin, emodin, chloroquine that regulate ROS and related molecular pathways in increasing CP sensitivity are described. Nanoparticles can provide co-delivery of CP with anti-tumor agents and by mediating photodynamic therapy, and induce ROS overgeneration to trigger CP sensitivity. Genetic tools, such as small interfering RNA (siRNA) can down-regulate molecular pathways such as HIF-1α and Nrf2 to promote ROS levels, leading to CP sensitivity. Considering the relationship between ROS and CP chemotherapy, and translating these findings to clinic can pave the way for effective treatment of cancer patients.
Item Type: Article
Uncontrolled Keywords: Anti-cancer therapy; Chemoresistance; Cisplatin; Drug resistance; Gene therapy; Nanoparticles; Reactive oxygen species
Divisions: Faculty of Engineering and Natural Sciences
Sabancı University Nanotechnology Research and Application Center
Depositing User: Ali Zarrabi
Date Deposited: 01 Sep 2022 23:15
Last Modified: 01 Sep 2022 23:15
URI: https://research.sabanciuniv.edu/id/eprint/43449

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