The study authors are Jayanth Suryanarayanan Shankaranarayanan, Jagat R. Kanwar, Afrah Jalil Abd AL-Juhaishi and Rupinder Kaur Kanwar.
The first author, Jayanth Suryanarayanan Shankaranarayanan, is a recent Deakin PhD graduate who is now working as postdoctoral fellow at the University of California, San Diego.
Dr Rupinder Kanwar, a senior research fellow with the Deakin Medical School’s Centre for Molecular and Medical Research, explained that doctors had stopped using Dox to treat prostate cancer because of the side-effects.
However, the results of this new research suggest that it may soon be possible to reintroduce Dox, coupled with lactoferrin, to the treatment regime – and make it even more effective than before.
“Dox is used widely for treating several types of cancers and is known for causing toxicity to the heart, brain and kidneys and for leading to cardiac arrest/heart failure,” Dr Kanwar said.
“Prostate cancer is one of the few cancers where chemotherapy is not the primary treatment. This is because these particular cancer cells are able to flush out the drug and become resistant to it, while the administered Dox continues to kill off the body’s normal cells, resulting in a range of side effects, the most damaging of which is heart failure. With this latest study, we have shown that by coupling Dox with lactoferrin the cancer cells take in the drug rather than pump it straight out. Lactoferrin is an iron-binding protein found in cow’s milk and human milk. It is known for its immune boosting and antimicrobial properties, making it an important part of the body’s protection against infection. It is also added as a key ingredient in baby formula.
Lactoferrin’s ability as an iron transporting protein – mopping up much-needed iron for growth of microbes (bacteria and parasites) from the site of infection – and its cancer cell killing activities have been exploited by the Deakin scientists to create an anti-cancer biodrug that has no side-effects and improves the immune system.
Previous work by the team with other types of cancer, funded by the Australia-India Strategic Research Fund (AISRF) to Professor Jagat Kanwar and Dr Kanwar, found that lactoferrin is not digested by the gut enzymes when fully saturated with iron and given as smart nanocapsules.
“We also developed MRI / CT scan-trackable, orally administered, smart nanocapsules, containing lactoferrin that can be taken by the blood directly to the cancer site,” Professor Jagat Kanwar said.
“This latest study builds on our previous work, whereby, to target toxicity and drug resistance, we coupled the Dox with lactoferrin, which was then fed to a particular breed of mice that naturally develop prostate cancer.
“Rather than being pumped out by the cancer cells, Dox was taken to these cells by lactoferrin through its receptors. It then stays in the nucleus of the cancer cells to perform its lethal action.
“Within 96 hours, all the cancer cells were dead when grown in 3D cancers in a culture dish from drug resistant and cancer stem cells. In feeding experiments, as an added benefit, there was an increase in red blood cells, white blood cells and haemoglobin, indicating that the immune system had also been boosted. Interestingly, this combination not only targeted the prostate tumour development in mice, it also led to repair of the Dox-induced damage to vital organs, including the heart and brain.
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