Cisplatin-a cancer treatment drug

The discovery of cisplatin

The use of the drug cisplatin as an anticancer drug was discovered by accident in 1965 by Dr. Barnett Rosenberg and his colleagues, Loretta VanCamp and Thomas Krigas, at Michigan State University in the USA. Rosenberg was investigating the effects of electric fields on bacterial growth using Escherichia coli (E. coli) bacteria. Platinum electrodes were used to pass the electric current through these bacterial cells since the team believed that platinum; being an unreactive metal would not interfere with the results of their experiments.

Rosenberg observed during his investigations that bacterial cell division was almost completely inhibited; which was a very surprising result indeed. Eventually after much research the cause of this inhibition of bacterial division was traced not to the electric fields used in his experiments but to a platinum containing compound formed by the electrodes during their experiments. This platinum compound was found to contain ammonia and chloride ligands.

Two possible compounds which could be inhibiting the bacterial cell division were identified as [Pt(NH₃)₂Cl₂] and [Pt(NH₃)₂Cl₄]. However further research proved that the active compound was in fact the diamminedichloroplatinum(II)-[Pt(NH₃)₂Cl₂] complex. Now this complex can exist as two geometric isomers, a cis and a trans isomer, the structure of these two isomers is shown in the image below:

After further investigation it was found that the trans isomer of diamminedichloroplatinum(II) was ineffective at stopping or reducing cell division and the actual active compound was the cis isomer of the diamminedichloroplatinum(II) complex, which was later renamed cisplatin. This square planar complex consists of a platinum ion (Pt²⁺) with two ammonia (NH₃) ligands and two chloride (Cl^-) ligands in a cis configuration. The "cis" prefix indicates that the ammonia and chloride ligands are positioned next to each other with the platinum ion at the centre of the complex, this cis arrangement is essential for its anticancer and biological activity.

Cisplatin action

• Activation: Cisplatin is given to the patient intravenously, it then enters the cancer cells by simple diffusion, once inside the cancer cells, where chloride ion concentration is low, the chloride ligands in the cisplatin complex are replaced by water molecules in a ligand exchange reaction, this change in ligands activates the cisplatin complex ion.
  
  
• DNA Binding: The activated cisplatin complex then binds to nitrogen atoms in one of the guanine bases in the cancer cells DNA, it forms cross-links, usually intrastrand cross-links between adjacent guanine bases present in the DNA. These cross-links distort the DNA structure, inhibiting further cell division. The inability of these cancer cells to repair their damaged DNA structure effectively results in the death of the cancer cell.

Side effects

• Kidney Damage: One of the main side effects of cisplatin use is kidney damage caused by the accumulation of cisplatin in the kidneys during chemotherapy. However the toxic effects on the kidneys can somewhat be managed by intravenous hydration before and after treatment with cisplatin.


• Other side effects include:
• Nausea and Vomiting:
• Neurotoxicity (nerve damage): Tingling or numbness in extremities such as fingers and toes may occur.
• Hearing loss, especially in younger patients, may occur.
• Hair Loss (alopecia): Cisplatin affects rapidly dividing hair follicle cells. The hair loss is typically not permanent and the hair usually regrows a few months after treatment ends.

Key Points

• Cisplatin is a highly effective in treating advanced ovarian cancer, bladder and small lung cancers. It is particularly effective at treating testicular cancer with a cure rates above 90%.


• Cisplatin forms cross-links between guanine bases in adjacent DNA strands and this distorts the DNA preventing any further replication and cell division, which ultimately results in cell death.


• One of the major side-effects of cisplatin treatment is the potential for long term kidney damage.

Check your understanding - Questions on cisplatin

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