Repurposing of idebenone as a potential anti-cancer agent
Repurposing of idebenone as a potential anti-cancer agent.
Glioblastoma (GB) represents the most common and aggressive form of malignant primary brain tumour associated with high rates of morbidity and mortality. In the present study, we considered the potential use of idebenone (IDE), a Coenzyme Q10 analogue, as a novel chemotherapeutic agent for GB. On two GB cell lines, U373MG and U87MG, IDE decreased the viable cell number and enhanced the cytotoxic effects of two known anti-proliferative agents: temozolomide and oxaliplatin. IDE also affected the clonogenic and migratory capacity of both GB cell lines, at 25 and 50 µM, a concentration equivalent to that transiently reached in plasma after oral intake that is deemed safe for humans. p21 protein expression was decreased in both cell lines, indicating that IDE likely exerts its effects through cell cycle dysregulation, and this was confirmed in U373MG cells only by flow cytometric cell cycle analysis which showed S-phase arrest. Caspase-3 protein expression was also significantly decreased in U373MG cells indicating IDE-induced apoptosis that was confirmed by flow cytometric Annexin V/propidium iodide staining. No major decrease in caspase-3 expression was observed in U87MG cells nor apoptosis as observed by flow cytometry analysis. Overall, the present study demonstrates that IDE has potential as an anti-proliferative agent for GB by interfering with several features of glioma pathogenesis such as proliferation and migration, and hence might be a drug that could be repurposed for aiding cancer treatments. Furthermore, the synergistic combinations of IDE with other agents aimed at different pathways involved in this type of cancer are promising. https://www.ncbi.nlm.nih.gov/pubmed/30602587
Idebenone is very interesting, I found a good price from my distributor in China.
I keep thinking about its low bioavailability:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853719/&source=gmail&ust=1563040974310000&usg=AFQjCNHrGPjAUaydkwNns4Soc6qyD5qE8 g"> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853719/
I am also worried about its mitochondrial action, from my humble ignorance I do not know if it is compatible with the mitochondrial inhibitors that we use.
I can use it together with the "empty liposomes" that I get and can improve its bioavailability.
I am going to publish in the forum all my reflections in the open section "gliosarcoma protocol".
I need help among all to correctly adjust the schedule of all drugs and infusions. After 8 months there seems to be a slight reduction now I must continue to deplete the cancer and reduce it.
The following additions will be: mitohonokiol, lomustine in very low doses + high doses of DHA ... liposomal idebenone? may orlistat to stop the oxidation of fatty acids as a tumor fuel .....
Thanks for all friend
The fact that your mom is in stable situation, possibly some regression, its great given how challenging is glioblastoma and the fact that one year ago it was advancing, before you started to treat it seriously and with such an extended strategy.
That means what you are doing now is working. So any change that you are doing should be done very careful. Don't turn directions fast - I know you did not wanted to do that but I just wanted to say this as I saw that when people have good results and want to push faster and more, the results may not be those desired. So step by step is the best way.
Regarding Idebenone, as I understand you may have the two actions: 1. on chloride channels, 2. on mitochondria. You are already using mito activators such as phenylbutyrate https://www.ncbi.nlm.nih.gov/pubmed/28450154 which acts like DCA ... while modulation of chloride channels could be very relevant in Glioblastoma:
Please read more on this subject as it is very important in Glioblastoma also for swelling and growth/death of tumors. As you will see in the second reference above Metformin helps on this line but there may be others that could help more.
Now I have to get ready for sleep as in a few hours I start a long drive to Romania.