A new way to attack cancer cells: target mitochondria with gold

Mitochondria are organelles within cells that are primarily energy-producing, like a kind of power plant. The food we eat and the oxygen we inhale go directly to the mitochondria to produce energy through a process called cellular respiration, which uses an energy unit called ATP. Just as the amount of electricity used is expressed in kilowatts, you can think of the energy in a living being as a measure of quantity. Researchers from the Department of Chemistry at the University of Kentucky published research results that inhibit the growth of cancer cells by using a method that attacks the mitochondria, a power plant located within the cancer cell, as the target in attacking cancer cells. And the used weapon was none other than gold.

Gold as a weapon in the fighting with cancer cells may sound unfamiliar to readers. Still, Cisplatin, the most famous anticancer drug, is the anticancer drug made of platinum. However, due to the drug resistance and toxic side effects of Cisplatin, anticancer drugs are being developed using many other metals. The University of Kentucky's Awuah Group is also one of the leading groups in developing anticancer drugs using gold. They synthesized compounds using gold and tried to target various cancer cells. The results were terrific. The results of the NCI-60 screening supported by the National Cancer Institute (NCI) showed that gold compounds effectively inhibited 60 different types of cancers. In particular, it showed excellent results with surprising lethal effects in central nervous system cancer (CNS), melanoma, and kidney cancer. Another peculiarity is the results show the different pharmacological actions shown by previous drug candidates. In other words, gold compounds have the potential as a whole new level of anticancer drugs, meaning that they have a different method of attacking cancer than other drug candidates previously reported.

The amount of gold compounds entering the cells was experimentally measured, and it was observed that the gold compounds enter the cancer cells and enter the mitochondria. It appears to be easily penetrated due to the two properties of gold compounds, positive charge, and lipophilicity. Specifically, when the experiment was conducted on normal cells, colon epithelial cells, the amount of gold compound penetrated was remarkably low.

The results of genetic analysis to confirm the attack route of gold compounds are very interesting. Among the genes of cancer cells treated by gold compounds, rheumatoid arthritis, oxidative phosphorylation, Parkinson's disease, cytokine receptor interactions, and NOD-like receptor signaling were included. Interestingly, these processes are mainly regulated by mitochondria and related to metabolism. This is associated with inflammation.

Therefore, the researchers evaluated the influence of gold compounds on mitochondria. In general, in mitochondria, oxygen is consumed, and ATP is produced. Therefore, this process of producing energy as oxygen is consumed is called cellular respiration (OXPHOS). By the way, the mitochondria of cancer cells affected by gold compounds consume oxygen, but there was a strange phenomenon that energy was not produced. This is a process called proton leakage, which is a defect in which the power plant works but does not produce energy. When this process intensifies, the cells eventually stop functioning due to a lack of energy. In addition, gold compounds were observed to disrupt the balance of electric charges formed inside and outside the mitochondria, preventing them from functioning properly. It was found experimentally that gold compounds attack mitochondria as a target, reducing the amount of energy supplied to cancer cells.

The results of animal experiments with mice are also very encouraging. The mice were implanted with 4T1 cells, a type of breast cancer, and then injected with a gold compound. As a result of observation for 20 days, in the case of mice injected with gold compounds, the growth of cancer cells was significantly suppressed. And during the same period, the weight of the mice slightly increased. This means that the drug is not toxic. When the gold compound was injected by intravenous injection, the compound was evenly distributed in each organ of the mice. And it showed the result of the accumulation of gold compounds in the tumor. The compound is considered to have a sustained effect by accumulating by lipophilicity.

In conclusion, gold compounds with previously unreported pharmacological action resulted in the inhibition of cancer cells, which seems to target mitochondria of cancer cells. The results of this study show the potential for the development of a new type of anticancer drug, and this study is still ongoing for the conversion of gold compounds into actual drugs.

This article is based on the following research paper:

Anticancer gold(iii)-bisphosphine complex alters the mitochondrial electron transport chain to induce in vivo tumor inhibition