Cancer is one such disease that is capable of spreading fear in almost all of mankind. It is widespread, has many different types and in often cases has no cure and difficult to treat. Since many centuries, extensive studies have been carried out in an effort to find a cure to this disease with studies showing significant developments in the last few days.
In ACS Applied Materials & Interfaces, researchers from Kanazawa University, Toyama Prefectural University, and BioSeeds Corporation describe the discovery of a chemical with increased antiproliferative action in cancer cells.
Vitamin D3 serves a variety of biological purposes, including preserving bone mineral density, which reduces the risk of fracture. Low vitamin D3 levels and the subsequent overproduction of an enzyme called CYP24 have been linked to a bad prognosis for cancer patients, hence vitamin D3 is thought to have anticancer properties. Chemicals that limit or inhibit the action of CYP24, as well as molecules that imitate the effect of vitamin D3, are now being studied as potential antiproliferative cancer treatments.
However, many of the inhibitors and D3 analogues that have been developed thus far have demonstrated insufficient clinical response as well as unwanted side effects. This study describes a DNAderived molecule that binds to and inhibits the function of CYP24 and has antiproliferative potential. The research team also goes into great detail on the underlying molecular processes at work.
The researchers studied a lot of DNA aptamers, which are single-stranded DNA fragments with specialised three-dimensional shapes that can attach to specific target molecules and have a functional impact. They focused on finding DNA aptamers that bind to CYP24 but not to CYP271B, which is responsible for vitamin D3 synthesis. A longlist of 18 aptamer candidates was narrowed down to 11 candidates with distinct molecular architectures. The 11 representative aptamers were tested in vitro for their ability to inhibit CYP24. Four candidates causing CYP24 inhibition but not CYP27B1 inhibition remained, one of which (Apt-7) was chosen for further research.
Apt-7 inhibits CYP24 activity, according to simulations and studies, and the aptamer presumably interferes with the enzyme’s active site. The researchers also used real-time high-speed atomic force microscopy to examine the binding of CYP24 and Apt-7, confirming the molecular docking situation they had predicted from simulations. Finally, the researchers investigated Apt-7’s biological effects by introducing the chemical into cancer cells. They discovered considerable CYP24 inhibition in a cancer cell line that had previously been found to overexpress the CYP24 enzyme, indicating antiproliferative action.
Madhu Biyani and colleagues who carried out this study remarked that these findings "clearly characterized and proposed that a DNA aptamer-based molecule could be a promising lead candidate for anticancer therapy."
With such developments, Cancer cure might just be on its way to becoming a reality and a sigh relief for millions around the world.
Reference:
Madhu Biyani et al, Novel DNA Aptamer for CYP24A1 Inhibition with Enhanced Antiproliferative Activity in Cancer Cells, ACS Applied Materials & Interfaces (2022).
Journal: ACS Applied Materials and Interfaces
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