Cisplatin, a drug with the ability to target and kill cancer cells, is a powerful weapon the fight against cancer.
One of the strongest arguments for basic research in science is that unexpected discoveries often result from exploring general topics. Such was the case for Barnett Rosenberg of Michigan State University, who in 1965 investigated whether electric fields would affect bacterial growth. His experiments revealed that when bacteria cells were exposed to electric fields, they would continue to grow – sometimes reaching up to 300 times their original size – but they also ceased to replicate. This unusual behavior was caused by the platinum electrodes he used to generate the electric field. Discovering a substance that would halt cell division led to the first highly effective platinum chemotherapy drugs.
Cisplatin, the compound from Rosenberg’s experiment, contains a platinum atom at the center of a square containing two chlorides and two NH3 (ammonia) groups. There are two different ways to arrange the groups on the platinum. The structure with two chlorides on adjacent corners of the square is cis-platin, whereas the arrangement with chloride atoms on opposite corners is a trans complex. Only the cis complex is an active antitumor agent because the platinum must bind to two adjacent locations on DNA. The specific DNA target site is two adjacent guanine groups, and when the platinum binds, it creates a kink in the DNA and partially unwinds the helix. These distortions prevent the cell from functioning properly and eventually kill the tumor cell.
Once the clinical efficacy of cisplatin was demonstrated several other platinum-based chemotherapy agents, such as carboplatin, were developed. This group of compounds is responsible for a better than 90 percent cure rate on testicular cancer, and they are used often in combination treatments of other cancers such as ovarian, head and neck, bladder, cervical, melanomas, and lymphomas.
A more extensive history and discussion of the chemistry of cisplatin may be found at http://pubs.acs.org/doi/abs/10.1021/ed083p728.
This topic was adapted from the technology milestones project of 2001 ACS President Attila Pavlath.