Mitochondria Could Represent A New Target For Cancer Therapy, According To New Study
A new breakthrough in cancer therapy suggests that the mitochondria may be targeted by future cancer therapies. Scientists from Chicago University were able to regulate the number of mitochondria in cancerous cells by manipulating two biochemical signals, thus obtaining a size reduction of human lung cancer transplanted into lab mice. Mitochondria represent the most important energetic structure of the cell, being involved in cellular metabolism.
When the cells begin to divide, mitochondria separate in two individual parts, process called fission. Once the division has ended, mitochondria will merge back into piece, process called fusion. Therefore, the dividing process requires one cell to increase its number of mitochondria by fission, resulting two parts of one mitochondria which will later on be included into two daughter cells.
Scientists were able to control molecular signals that regulate the process of fission and fusion in malignant cells, thus reducing cell division and stopping cancerous cell proliferation (the most important characteristic of cancer development). By increasing the signals that stimulate fusion, researchers were able to achieve tumor reduction by one-third of the original size. Using molecular signals that inhibit fission the tumor was reduced with more than a half of its original size.
“We found that human lung cancer cell lines have an imbalance of signals that tilts them towards mitochondrial fission. By boosting the fusion signal or blocking the fission signal we were able to tip the balance the other way, reducing cancer cell growth and increasing cell death. We believe this provides a promising new approach to cancer treatment.”, according to researchers.
With this study scientists proved that a huge step forward in cancer treatment can be achieved by targeting mitochondrial division. Stopping the division process of mitochondria stops the entire cell division. Until now, drugs used in cancer treatments interfere with the whole cell division process. This new therapy interferes only with mitochondrial division and will probably prove to be very useful for treating patients suffering from types of cancers that become resistant to drugs that are targeting the cellular cycle.
Researchers observed that malignant cells present an fragmented mitochondrial internal network compared to normal cells. It was noticed that cancerous cells also present low leveles of one protein that stimulates fusion, called mitofusin-2 (Mfn-2) and high levels of a protein that promotes fission, called dynamin-related protein (Drp-1). Drp-1 has a very important role in mitochondrial division at the beginning of the fission process. High levels of this protein are surrounding mitochondria causing their separation into two fragments.
Scientists used gene therapy to inhibit fission by increasing the activity of Mfn-2 and inhibit Drp-1 both by altering the production and injecting a molecule that interferes with its activity. After these interventions, researchers concluded that inhibiting Drp-1 does not represent a cancer cure. Although tumor size does decrease, the treatment fails in making it disappear altogether.
“Inhibiting mitochondrial fission did not show any significant toxicity in mice or rats, so we are quite optimistic that our findings can lead to the development of novel, clinically feasible therapies.”, researchers added.
These therapies which promote the activity of Mfn-2 and inhibit the activity of Drp-1 are only available for laboratory studies and have not yet been tested on humans. Perhaps clinical trials will evaluate these treatment options in the near future.