Cisplatin-Based Chemotherapy of Human Cancers

Abstract

Cisplatin (cis-diammine-dichloro-platinum II) was initially discovered to prevent the growth of Escherichia coli and was further recognized for its anti-neoplastic and cytotoxic effects on cancer cells. Administered intravenously to humans, cisplatin is used as first-line chemotherapy treatment for patients diagnosed with various types of malignancies, such as leukemia, lymphomas, breast, testicular, ovarian, head and neck, and cervical cancers, and sarcomas. Once cisplatin enters the cell it exerts its cytotoxic effect by losing one chloride ligand, binding to DNA to form intra-strand DNA adducts, and inhibiting DNA synthesis and cell growth. The DNA lesions formed from cisplatin-induced DNA damage activate DNA repair response via NER (nuclear excision repair system) by halting cisplatin-induced cell death by activation of ATM (ataxia telangiectasia mutated) pathway. Although treatment has been shown to be effective, many patients experience relapse due to drug resistance. As a result, other platinum compounds such as oxaliplatin and carboplatin have since been used and have shown some levels of effectiveness. In this review, the clinical applications of cisplatin are discussed with a special emphasis on its use in cancer chemotherapy.

Keywords: Cancer chemotherapy; Cisplatin; Human cancers; Platinum-based dugs.

Figure 1

Molecular structure of cisplatin: This platinum compound is centered around two adjacent chloride ligands (on the left) and two amine groups (on the right).

Figure 2

Overview of molecular mechanisms of cisplatin cytotoxicity: Cisplatin enters into cancer cells and interacts with DNA to form DNA adducts. It regulates protein kinase (ATM) and activates p53 leading to a series of signaling cascade and apoptosis in cancer cells.