Fungal compound as an anticancer drug

Scientists from Tokyo University have synthesised a fungal molecule which is able to induce cell death in aggressive cancers

One key hallmark of cancer is the ability to resist programmed cell death – apoptosis. Unlike healthy cells which divide a specific number of times before they die, cancer cells are able to keep dividing to form a large mass of cells known as a tumour.

Apoptosis is governed by many genes which work together to ensure the process is successfully executed. Often referred to as the “guardian of the genome”, p53 is one of the most important proteins involved in apoptosis. It scans the cell for problems which have the potential to result in cancer formation, including DNA damage and aberrant oncogene activation.

Oncogenes are sequences of DNA which, when overexpressed in a cell, can cause cancer. p53 is a tumour suppressor gene, which works to prevent cancer. It is often activated when oncogenes become mutated, in order to counter their effects. If p53 itself is mutated it is unable to function as a tumour suppressor and the cell is more likely to ‘transform’ and become cancerous. This often happens in the early stages of lung, head and neck and skin cancers which are associated with a poor prognosis.

Previously, scientists found an anticancer protein called FE399 in a species of filamentous fungus, Ascochyta. This protein was able to induce apoptosis in human colorectal cancer cells, especially those with a mutated p53 protein.

For a variety of reasons, researchers struggled to purify this protein from the fungus itself in order to make use of it as an anticancer drug. The team of scientists from Tokyo decided to start from scratch and synthesise the protein compound from existing precursors in the lab. This took many rounds of construction and purification, resulting in very similar proteins with an almost identical structure. Sifting through these different isomers, the team’s efforts payed off when they found three spots on a petri dish with an identical structure and chemical composition to FE399.

The scientists are confident that their research will transform the way colorectal cancer is treated in the future. They are hopeful too, that this compound will prove effective against other solid and blood cancers which are fuelled by a mutation in p53. Further research is needed to test the efficacy of this protein compound, however if successful, it will have the potential to change people’s lives.

Reference:

  1. Takayuki Tonoi, Miyuki Ikeda, Teruyuki Sato, Takehiko Inohana, Ryo Kawahara, Takatsugu Murata, Isamu Shiina. Total Synthesis of the Antitumor Depsipeptide FE399 and its S-Benzyl Derivative:A Macrolactamization Approach. European Journal of Organic Chemistry, 2020; DOI: 10.1002/ejoc.202000459

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