estructura-casiopeinas-2

Image: Molecular structure of casiopeína / Source: Agencia Informativa CONACYT

The family of anticancer complexes designed in Mexico that include the transition metal copper known as Casiopeínas has shown benefits in the treatment of cancer, particularly by increasing specificity and decreasing side effects in comparison to current drugs.

The main effect that casiopeínas have demonstrated in the fight against cancer is a cytotoxic effect by activation of pro-apoptotic processes in malignant cells. Apoptosis is the process of programmed cell death — one of the checks and balances built into the cell cycle — which helps destroying mutated cells, preventing the development of cancer.

In the article “Network analysis shows novel Molecular Mechanisms of action for copper-based chemotherapy,” published in the journal Frontiers in Physiology, it was reported the physiological responses of cervical cancer cell cultures to Casiopeína II-gly (CasII-gly).

This research allowed us to know that, besides producing pro-apoptotic processes in malignant cells, the drug also produces other effects on cells:

  • Cell cycle inhibition: the drug prevents malignant cells to continue with their life cycle, by inhibiting estrogen-mediated G1/S cell cycle progression.
  • Downregulates transformation processes in fibroblasts: fibroblasts are cells involved in the formation of the extracellular matrix. In cancer, they can contribute to tumor growth, tissue invasion, and vascularization. The drug reduces the multiplication of these cells.
  • Decreases cellular migration events: CasII-gly inhibited uncontrolled cell migration of cancer cells. This is important, because migration of malignant cells can lead to metastasis or invasion of healthy tissues.
  • Showed increased molecular mechanisms of liver protection: one of the most damaging side effects of chemotherapy is its toxic effect on the liver. Sometimes, liver damage caused by chemotherapy drugs is more dangerous than the tumor itself. The molecular mechanisms of liver protection are increased in the cell cultures under the actions of Casiopeínas, unlike the case in many other cytotoxic drugs.

The researchers also found evidence that this drug could activate the body’s general immune response, as well as repair mechanisms of damaged cells.

All these effects were studied by detecting molecules that the cells produced or stopped producing when perform an action, such as liver protection, migration, cell division.

Based in their discoveries, the group of researchers was able to conclude that a therapy based on CasII-gly can prevent the problematic side effects of chemotherapy, which often compromise the health of patients.

Casiopeínas contain a copper atom in their structure, which makes them highly reactive to genetic material. However, unlike the toxicity that other metals cause in the body, as copper is a naturally occurring element in our cells, it can be handled and disposed more easily by the body.

Research on the mechanisms of action of these anti-cancer compounds is not over. Now, a group of scientists at the National Institute of Genomic Medicine (INMEGEN) of the National Autonomous University of Mexico (UNAM) and the Autonomous University of Queretaro conducts clinical trials to measure the toxicity of this drug in humans.

Currently, (the drug) is in the process called phase I clinical trials, which is a testing phase to observe its toxicity in humans. One thing is that it works well in cellular and animal models, and another is evaluating its possible side effects in humans. Once the drug is validated at this stage, there still is a couple of even stricter phases, before its use in humans can be approved,” said Dr. Enrique Hernandez Lemus, deputy director of Population Genomics at INMEGEN.

Regarding the possible mechanisms of drug action, Hernandez Lemus talked about other studies that the research group is currently performing.

In addition to the experimental work in medicinal chemistry and toxicology, the working group — which includes several leading researchers and dozens of students — has developed theoretical and computational studies, from both the point of view of the biological mechanisms through genomics and biology systems, and from the physicochemical point of view through quantum chemistry and molecular dynamics.”

We now know that there are at least two ways by which these drugs operate on tumor cells: by direct intercalation into these cells’ DNA; and through biochemical mechanisms that lead the cell into a programmed cell death (apoptosis). However, we are still considering which other effects they can have, in both healthy cells and tumors,” he said.

 

Source: Agencia Informativa CONACYT