This is a continuation of cancer as a metabolic disease due to mitochondrial dysfunction. We will discuss our initial work on the Mitochondrial Organelle Transplantation.
I stated on the last post about cancer as a metabolic disease and some of the results of our mitochondrial organelle transplantation would be presented. I am sorry I am a little late in posting this but I have been on a research trip to discuss collaboration with Hebert Weissbach, PhD, at Florida Atlantic University.
When I initially thought that mitochondria as bacteria could be isolated from normal cells, I told my research associates what I wanted to do about isolating normal mitochondria to see if they might enter cancer cells in cell culture. They first thought that I was dreaming about something that was probably never going to happen; however, Mr. Jiang agreed to order a mitochondrial isolation kit and we decided to go ahead and isolate mitochondria from a normal human mammary epithelial cell line. We stained the cells before isolation with a stain that is a vital stain that the mitochondria will not take up unless they are functioning well. That stain is called JC-1. When Mr. Jiang initially isolated the mitochondria, and incubated them with some cancer cells lines he immediately after he looked at this under a fluorescent microscope came to get me to come into the lab to observe. We were extremely excited that yes, normal mitochondria could be isolated, stained with a vital stain JC-1, co-incubate with cancer cells and ENTER the cancer cells. This was proven by fluorescent microscopy. I next postulated that possibly if normal mitochondria would enter cancer cells they possibly may reverse their metabolism from glycolysis to oxidative phosphorylation which is normal cellular respiration. Possibly inhibit proliferation. In so doing might even make these cancer cells more responsive to chemotherapy agents.
The next procedure we did was to incubate the normal mitochondria with cancer cell lines and test for inhibited cellular proliferation. That requires a proliferation assay that requires radioactive thymidine which is involved in DNA synthesis. The final results are obtained in a radiation scintillation counter by certain amounts of counts. Knowing if you have a high count you have a lot of cellular proliferation and DNA synthesis. If you have low counts you have inhibited the proliferation. Mr. Jiang set up the procedure and as I came in one Saturday morning to do the normal Saturday morning work I decided to go into the lab to see if anything had come off of the scintillation counter and I found a large strip of data. I read the results of this data and although I do not do this very much and have not been technically associated with this procedure, it looked to me as if proliferation in the cancer cells after being co-cultured with normal mitochondria and the mitochondria entering the cancer cells had definitely inhibited proliferation. I went home that day quite excited and it was almost too hard to believe and could not wait for Monday morning to come to talk with Mr. Jiang. I left a message for him to get in touch with me Monday morning as soon as he came in.
We looked at the data and he agreed that it showed inhibition of cellular proliferation in the cancer cell line. However, he was still doubtful and reluctant to accept this data and he said he wanted to repeat this experiment 3 more times. He did repeat it 3 more times and the exact same results were obtained; it definitely inhibited the cancer cell proliferation. What was the mechanism?
Therefore, we decided the next experiment we would repeat the same experiment but this time after so many days we could change the media and test the drug sensitivity. We found after co-incubating the cancer cells with normal mitochondria not only inhibited proliferation, but also increased tremendously drug sensitivity. In essence, it makes drugs more responsive and made the cancer cells more responsive to chemotherapy agents increasing their sensitivity indicating that in a patient possibly this would mean you could give a lot less drug, get the same effect, and maybe even a better effect, and cut down on a lot of the toxicity from chemotherapy.
This finding was extremely exciting and after repeating the experiment many more times, we decided to publish our first paper in the Breast Cancer Research and Treatment Journal on “Mitochondria organelle transplantation: introduction of normal epithelial mitochondria into human cancer cells inhibits proliferation and increases drug sensitivity” in 2012.
We have had a tremendous response to that paper, and more research has been done since that time and we will be presenting further results of this research in future posts. Thank you for reading and please if you would like to contribute to support our research, visit the Donate page on our Blog website. This is getting very exciting and it is ground breaking new research for cellular biotherapy especially in cancer. As a short note, we feel like mitochondrial organelle transplantation may also play a significant role in neurodegenerative diseases and we will mention that in later posts.
Robert L. Elliott, M.D., Ph.D., D.Sc.