Scientists have forced cancer cells to self-destruct

MitoTam is a modification of an older medication called Tamoxifen, which is regularly used against breast cancer, but is effective only with certain types of the cancer. More aggressive forms of breast cancer are resistant to it. Researchers from the BIOCEV research centre in Vestec u Prahy have decided to try a counter-attack. They found the Achilles’ heel of cancer cells – their mitochondria, or cellular power plants, that supply them with energy. By targeting MitoTam on mitochondria, they can literally force the cells to kill themselves.

"We have found that the new MitoTam agent, a mitochondria-targeted derivative of tamoxifen, an anticancer agent, is very effective against breast cancer cells with a high expression of HER2 oncoprotein where original tamoxifen is ineffective. Moreover, our agent is also very effective against “triple negative” forms of breast cancer that are totally incurable at the moment,” explains Kateřina Rohlenová from the Institute of Biotechnology of the Czech Academy of Sciences, which is based in the BIOCEV Centre. "One of the reasons why MitoTam is very effective against breast cancer with a high level of HER2 oncoprotein is the high level of this protein in cancer cell mitochondria, which is a rather surprising finding. MitoTam inhibits complex I in the mitochondrial respiratory chain, which triggers the production of oxygen radicals that are toxic to the cell. As a result, this launches a cascade of actions that cause programmed cell death, known as apoptosis. We have proven that forms of cancer with a high level of HER2 show increased respiration in complex I, which makes these cells exceptionally sensitive to MitoTam. The mechanism of MitoTam effectiveness, targeted at cancer cell mitochondria and their respiratory chain, is not dependent on the expression of any specific oncoprotein. Our results show that it is an extraordinarily effective agent that, in theory, might be used against other types of cancer,” adds the young researchers and the key person of this several-year-long project being investigated by an international team led by Prof. Jiří Neužil from the Institute of Biotechnology, the Czech Academy of Sciences, and Griffith University in Australia. The importance of this discovery is also evidenced by an article that has been published in the prestigious Antioxidants & Redox Signaling journal. One of the microscopic images taken by the team appears on the cover page of the journal.

The first stage of MitoTam testing will verify whether or not it is toxic to the human body. The second stage counts on the participation of several dozen of patients. According to the regulations, two more stages have to follow that involve a high number of patients and international involvement. The entire process may last several years, but researchers are optimistic. "Results up to now show that MitoTam has very good potential to become an effective anticancer agent,” says Rohlenová.

For more information, see the publication: http://online.liebertpub.com/doi/full/10.1089/ars.2016.6677

Publication:

Rohlenova, K., Sachaphibulkij, K., Stursa, J., Bezawork-Geleta, A., Blecha, J., Endaya, B., Werner, L., Cerny, J., Zobalova, R., Goodwin, J., Spacek, T., Alizadeh, P. E., Yan, B., Nguyen, M. N., Vondrusova, M., Sobol, M., Jezek, P., Hozak, P., Truksa, J., Rohlena, J., Dong, L.-F., Neuzil, J. Selective Disruption of Respiratory Supercomplexes as a New Strategy to Suppress Her2high Breast Cancer . Antioxidants & Redox Signaling, 26(2): 84-103, 2017. doi: 10.1089/ars.2016.6677.