Curcumin and its derivatives in cancer therapy: Potentiating antitumor activity of cisplatin and reducing side effects.

Asal Jalal Abadi, Sepideh Mirzaei, Mahmood Khaksary Mahabady, Farid Hashemi, Amirhossein Zabolian, Fardin Hashemi, Pourya Raee, Shahin Aghamiri, Milad Ashrafizadeh, Amir Reza Aref, Michael R Hamblin, Kiavash Hushmandi, Ali Zarrabi, Gautam Sethi

Journal: Phytotherapy research : PTR 2022;36(1):189-213

PMID: 34697839

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Abstract

Curcumin is a phytochemical isolated from Curcuma longa with potent tumor-suppressor activity, which has shown significant efficacy in pre-clinical and clinical studies. Curcumin stimulates cell death, triggers cycle arrest, and suppresses oncogenic pathways, thereby suppressing cancer progression. Cisplatin (CP) stimulates DNA damage and apoptosis in cancer chemotherapy. However, CP has adverse effects on several organs of the body, and drug resistance is frequently observed. The purpose of the present review is to show the function of curcumin in decreasing CP's adverse impacts and improving its antitumor activity. Curcumin administration reduces ROS levels to prevent apoptosis in normal cells. Furthermore, curcumin can inhibit inflammation via down-regulation of NF-κB to maintain the normal function of organs. Curcumin and its nanoformulations can reduce the hepatoxicity, neurotoxicity, renal toxicity, ototoxicity, and cardiotoxicity caused by CP. Notably, curcumin potentiates CP cytotoxicity via mediating cell death and cycle arrest. Besides, curcumin suppresses the STAT3 and NF-ĸB as tumor-promoting pathways, to enhance CP sensitivity and prevent drug resistance. The targeted delivery of curcumin and CP to tumor cells can be mediated nanostructures. In addition, curcumin derivatives are also able to reduce CP-mediated side effects, and increase CP cytotoxicity against various cancer types.

Address: Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.; Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran.; Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran.; Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.; Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.; School of Rehabilitation, Department of Physical Therapy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.; Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.; Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.; Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.; Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Tuzla, Turkey.; Sabanci University Nanotechnology Research and Application Center (SUNUM), Istanbul, Turkey.; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.; Vice President at Translational Sciences, Xsphera Biosciences Inc, Boston, Massachusetts, USA.; Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa.; Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran.; Department of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.; Sabanci University Nanotechnology Research and Application Center (SUNUM), Istanbul, Turkey.; Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Sariyer, Istanbul, Turkey.; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

DOI: 10.1002/ptr.7305

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MeSH Terms: Antineoplastic Agents, Apoptosis, Cisplatin, Curcumin, Humans, Neoplasms