An integrative review of Cisplatin: the first metal Anti-Tumor drug.

  • Arvind Singh Jadon School of Studies in Pharmaceutical Sciences, Jiwaji University, Gwalior, Madhya Pradesh.
  • Poonam Bhadauriya Gurukul Institute of Pharmaceutical Science & Research, Gwalior, Madhya Pradesh.
  • Manoj Sharma School of Studies in Pharmaceutical Sciences, Jiwaji University, Gwalior, Madhya Pradesh.


Cisplatin and other platinum derivatives like carboplatin and oxaliplatin are widely used chemotherapeutic agents used in the treatment of solid tumors including head and neck, ovarian and testicular germ cell tumors. Cisplatin is also used successfully in the treatment of paediatric malignancies, such as medulloblastoma and osteogenic sarcoma. In most recent treatment schedules, the drug is used in combination with other cytotoxic agents such as otoposide, doxorubicine, paclitaxel, 5-fluorouracil, gemcitabine, vinblastine, bleomycin and others. It is one of on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in health system. This comprehensive review highlights the physicochemical properties of cisplatin and related platinum based drugs, uses of platinum, either alone or in combination with other drugs for the treatment of various human cancers and also discuss about various Potential protective strategies against cisplatin-induced cytotoxicities. A special attention is given to it’s molecular mechanisms of action, historical background, undesirable side effects & future prospective.

Keywords: Cisplatin, cytotoxicity, cis-diamminedichloroplatinum.


Download data is not yet available.

Author Biographies

Arvind Singh Jadon, School of Studies in Pharmaceutical Sciences, Jiwaji University, Gwalior, Madhya Pradesh.

School of Studies in Pharmaceutical Sciences, Jiwaji University, Gwalior, Madhya Pradesh.

Poonam Bhadauriya, Gurukul Institute of Pharmaceutical Science & Research, Gwalior, Madhya Pradesh.

Gurukul Institute of Pharmaceutical Science & Research, Gwalior, Madhya Pradesh.

Manoj Sharma, School of Studies in Pharmaceutical Sciences, Jiwaji University, Gwalior, Madhya Pradesh.

School of Studies in Pharmaceutical Sciences, Jiwaji University, Gwalior, Madhya Pradesh.


1. Uppuluri S, Ali SL, Nirmala T, Shanthi M, Sipay B, Uppuluri KB. Nephroprotector activity of hydro alcoholic extract of Tinospora cordifolia roots on cisplatin induced nephrotoxicity in rats. Drug Invent Today 2013; 5 (4):281–287.
2. Pabla N, Dong Z. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int 2008; 73 (9):994–1007
3. Reedijk J, Lohman PHM. Cisplatin: synthesis, antitumour activity and mechanism of action. Pharm. World Sci 1985; 7(7):173–180.
4. Dos Santos NAG, Rodrigues MAC, Martins NM, Dos Santos AC. Cisplatin-induced nephrotoxicity and targets of nephroprotection: an update. Arch. Toxicol 2012; 86 (8):1233–1250.
5. Florea AM and Busselberg D. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancer 2011; 3 (1):1351–1371.
6. Peyrone, M. "Ueber die Einwirkung des Ammoniaks auf Platinchlorür" [On the action of ammonia on platinum chloride]. Ann Chem Pharm 1844; 51 (1):01–29.
7. Rosenberg B, Vancamp L, Krigas, T. Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode. Nature 1965; 205 (4972):698–699
8. Rosenberg B, Van Camp L, Trosko JE, Mansour V H. Platinum compounds: a new class of potent antitumour agents. Nature 1969; 222 (5191):385–386.
9. Wang D & Lippard SJ. Cellular processing of platinum anticancer drugs. Nat Rev Drug Discov 2005; 4:307-320.
10. IARC. 1981. Cisplatin. In Some Antineoplastic and Immunosuppressive Agents. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 26. Lyon, France: International Agency for Research on Cancer. 151-164.
11. Akron. 2009. The Chemical Database. The Department of Chemistry at the University of Akron.
12. Kortmann RD, et al. Current and future strategies in radiotherapy of childhood low grade glioma of the brain Part I: Treatment modalities of radiation therapy. Strahlenther Onkol 2003; 179:509-520.
13. Kang H, Kim TJ, Kim WY, Choi CH, Lee JW, Kim BG, Bae DS. Outcome and reproductive function after cumulative high-dose combination chemotherapy with bleomycin, etoposide and cisplatin (BEP) for patients with ovarian endodermal sinus tumor. Gynecol Oncol 2008; 111:106-110.
14. Motte DL, Rouge T, et al. Survival and reproductive function of 52 women treated with surgery and bleomycin, etoposide, cisplatin (BEP) chemotherapy for ovarian yolk sac tumor. Ann Oncol 2008; 19:1435-1441.
15. Cheng X, Developing Organic and Inorganic Nanomedicine for Cancer Therapy. Journal of Drug Delivery and Therapeutics, 2017; 7(2):1-4.
16. Alderden RA, Hall MD, Hambley TW. The Discovery and Development of Cisplatin. J Chem Educ 2006; 83 (5):728-734.
17. SRI. 2009. Directory of Chemical Producers. Menlo Park, CA: SRI Consulting. Database edition.
18. ChemSources. 2009. Chem Sources - Chemical Search. Chemical Sources International. http://www.chemsources .com/chemonline.html and search on cisplatin.
19. FDA. 2009. The Electronic Orange Book. U.S. Food and Drug Administration. and select Search by Active Ingredient and search on cisplatin.
20. Dasari S & Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 2014; 740:364–378.
21. Yang Z, Schumaker LM, Egorin MJ, Zuhowski EG, Guo Z, Cullen KJ. Cisplatin preferentially binds mitochondrial DNA and voltage-dependent anion channel protein in the mitochondrial membrane of head and neck squamous cell carcinoma: possible role in apoptosis. Clin Cancer Res 2006; 12:5817-5825.
22. Jordan P & Carmo-Fonseca M. Cisplatin inhibits synthesis of ribosomal RNA in vivo. Nucleic Acids Res 1998; 26: 2831-2836.
23. Cullen KJ, Yang Z, Schumaker L, Guo Z. Mitochondria as a critical target of the chemotheraputic agent cisplatin in head and neck cancer. J Bioenerg Biomembr 2007; 39:43–50.
24. Inoue K., et al. Cisplatin-induced macroautophagy occurs prior to apoptosis in proximal tubules in vivo. Clin Exp Nephrol 2009; 14:112-122.
25. Kelland L. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 2007; 7:573-584.
26. Pabla N. & Dong Z. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int 2008; 73:994-1007.
27. Siddik ZH. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 2003; 22:7265–7279.
28. Wernyj RP, Morin PJ. Molecular mechanisms of platinum resistance: still searching for the Achilles’ heel. Drug Resist Updat 2004; 7:227–232.
29. De Jongh FE, Van Veen RN, Veltman SJ, de WR, Vander Burg ME, Van den Bent MJ, Planting AS, Graveland WJ, Stoter G, Verweij J. Weekly high-dose cisplatin is a feasible treatment option: analysis on prognostic factors for toxicity in 400 patients. Br J Cancer 2003; 88:1199–1206.
30. Al-Majed AA. Carnitine deficiency provokes cisplatin-induced hepatotoxicity in rats. Basic Clin Pharmacol Toxicol 2007; 100:145–150.
31. Yousef MI, Saad AA, El-Shennawy LK. Protective effect of grape seed proanthocyanidin extract against oxidative stress induced by cisplatin in rats. Food Chem Toxicol 2009; 47:1176–1183.
32. Kart A, Cigremis Y, Karaman M, Ozen H. Caffeic acid phenethyl ester (CAPE) ameliorates cisplatininduced hepatotoxicity in rabbit. Exp Toxicol Pathol 2010; 62:45–52.
33. Miller RP, Tadagavadi RK, Ramesh G, Reeves WB, Mechanisms of cisplatin nephrotoxicity. Toxins 2010; 2(11): 2490–2518.
34. Purena R, Seth R, Bhatt R, Protective role of Emblica officinalis hydro-ethanolic leaf extract in cisplatin induced nephrotoxicity in Rats. Toxicology Reports 2018; 5:270–277.
35. Forbes JM, Coughlan MT, Cooper ME. Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes 2008; 57:1446-1454.
36. Nistala R, Whaley-Connell A, Sowers JR. Redox control of renal function and hypertension. Antioxid Redox Signal 2008; 10:2047-2089.
37. Heyman SN, Rosen S, Rosenberger C. A role for oxidative stress. Contrib Nephrol 2011; 174:138-148.
38. Manucha W & Valles PG. Apoptosis modulated by oxidative stress and inflammation during obstructive nephropathy. Inflamm Allergy Drug Targets 2012; 11:303-312.
39. Avan A, Postma TJ, Ceresa C, Avan A, Cavaletti G, Giovannetti E, Peters GJ. Platinum-induced neurotoxicity and preventive strategies: past, present, and future. Oncologist 2015; 20:411–432.
40. Carozzi VA, Canta A, Chiorazzi A. Chemotherapy-induced peripheral neuropathy: What do we know about mechanisms? Neurosci Lett 2015; 596:90–107.
41. Milosavljevic N, Duranton C, Djerbi N, Puech PH, Gounon P, Lagadic-Gossmann D, et al. Nongenomic effects of cisplatin: acute inhibition of mechanosensitive transporters and channels without actin remodeling. Cancer Res 2010; 70 (19):7514–7522.
42. Fauser AA, Fellhauer M, Hoffman M, Link H. Guidelines for anti-emetic therapy: acute emesis. Eur J Cancer 1999; 35:361-370.
43. Iraz M, Kalcioglu MT, Kizilay A, Karatas E. Aminoguanidine prevents ototoxicity induced by cisplatin in rats. Ann Clin Lab Sci 2005; 35:329–335.
44. Longchar A and Prasad SB. Ascorbic acid (vitamin c) ameliorates cisplatin induced hematotoxicity in tumor-bearing mice. World J of Phar and Pharmaceutical Sci 2016; 5 (4):1870-1891
45. Levi JA, Aroney RS, Dalley DN. Haemolytic anaemia after cisplatin treatment. Br Med J 1981; 282 (6281): 2003–2004.
46. Hartmann JT & Lipp HP. Toxicity of platinum compounds. Expert Opin Pharmacother 2003; 4:889– 901.
47. Pasetto LM, DAndrea MR, Brandes AA, et al. The development of platinum compounds and their possible combination. Crit Rev Oncol Hematol 2006; 60:59–75.
48. Screnci D & McKeage M. Platinum neurotoxicity: clinical profiles, experimental models and neuroprotective approaches. J Inorg Biochem 1999; 77:105-110.
49. Cornelison TL, Reed E. Nephrotoxicity and hydration management for cisplatin, carboplatin, and ormaplatin. Gynecol Oncol 1993; 50:147–158.
50. Bajorin DF, Bosl GJ, Alcock NW et al. Pharmacokinetics of cis-diamminedichloroplatinum(II) after administration in hypertonic saline. Cancer Res 1986; 46:5969–5972.
51. Franke RM, Kosloske AM, Lancaster CS, et al. Influence of Oct1/Oct2-deficiency on cisplatin-induced changes in urinary N-Acetyl-{beta}-D-Glucosaminidase. Clin Cancer Res 2010; 16:4198–4206.
52. Sprowl JA and Sparreboom A. Special Section on Transporters in Toxicity and Disease Minireview Uptake Carriers and Oncology Drug Safety. Drug Metab Dispos 2014; 42:611-622.
53. Kim HJ, Park DJ, Kim JH, et al. Glutamine protects against cisplatin-induced nephrotoxicity by decreasing cisplatin accumulation. J Pharmacol Sci 2015; 127:117–26.
54. El-Awady SE, Moustafa YM, Abo-Elmatty DM, Radwan A. Cisplatin-induced cardiotoxicity: mechanisms and cardioprotective strategies. Eur J Pharmacol 2011; 650:335–41.
55. Chiarandini Fiore JP, Fanelli SL, de Ferreyra EC, Castro JA. Diallyl disulfide prevention of cis-Diamminedichloro platinum-induced nephrotoxicity and leukopenia in rats: potential adjuvant effects. Nutr Cancer 2008; 60:784–791.
56. Fard AA, Ahangarpour A, Gharibnaseri KM, Ahmadizadeh M, Rashidi I, Jalali T. Effects of exogenous and endogenous hydrogen sulfide on plasma renin and erythropoietin in cisplatin-induced nephrotoxicity in rats. URMIAMJ 2015; 26:459–466.
57. Longchar A and Prasad SB. Biochemical changes associated with ascorbic acid–cisplatin combination therapeutic efficacy and protective effect on cisplatin-induced toxicity in tumor-bearing mice. Toxicol Rep 2015; 2:489–503.
58. Ahangarpour A, Fard AA, Gharibnaseri MK, Jalali T, Rashidi I. Hydrogen sulfide ameliorates the kidney dysfunction and damage in cisplatin induced nephrotoxicity in rat. Vet Res Forum 2014; 5:121–127.
59. Ahmad A, Olah G, Szczesny B, Wood ME, Whiteman M, Szabo C. AP39, A mitochondrially targeted hydrogen sulfide donor, exerts protective effects in renal epithelial cells subjected to oxidative stress in vitro and in acute renal injury in vivo. Shock 2016; 45(1): 88–97.
60. Ansari SB, Kurian GA. Hydrogen sulfide modulates sub-cellular susceptibility to oxidative stress induced by myocardial ischemic reperfusion injury. Chem Biol Interact 2016; 252: 28–35.
61. Strutynska NA, Dorofeieva NO, Vavilova HL, Sahach VF. Hydrogen sulfide inhibits Ca(2+)-induced mitochondrial permeability transition pore opening in spontaneously hypertensive rats. Fiziol Zh 2013; 59:03–10.
1 Views | 4 Downloads
How to Cite
Jadon, A. S., Bhadauriya, P., & Sharma, M. (2019). An integrative review of Cisplatin: the first metal Anti-Tumor drug. Journal of Drug Delivery and Therapeutics, 9(3), 673-677.