TRAIL mimics: A multidisciplinary approach to killing cancer cells
Scientists at the Aoki Laboratory, headed by Professor Shin Aoki, at Tokyo University of Science have taken a giant leap in the battle against cancer. They have synthesized an artificial protein that can kill cancer cells.
This study undertaken by the Pharmaceutical sciences lab in Tokyo University of Science aims to reduce the probability of cancer metastasis and reduce anxiety in cancer patients.
According to the World Health Organization, there were 18.1 million new cases of cancer and 9.6 million fatalities worldwide in 2018. Cancer is the second leading cause of death globally. This emperor of maladies that afflicts over 10% of the world’s population is the collective focal point of cutting-edge research by teams of scientists across the world.
Among the core issues that have perplexed scientists are how to effectively destroy cancer cells, and how to create simple and convenient methods to trap, culture, and re-collect cancer cells for further study. Scientists at the Aoki Laboratory, Tokyo University of Science (TUS), have, in a series of papers published recently, managed to advance our understanding of both problems.
The Aoki Lab works in several inter-related scientific areas, and it is this multidisciplinary approach that allows it to look at combating cancer from different angles. “A disease like cancer needs tackling from all directions,” remarked Professor Shin Aoki, who heads Aoki Lab, “and so, my team works at the intersection of pharmaceutical sciences, organic chemistry, bioinorganic chemistry, and supramolecular chemistry.” Commenting specifically on the research behind the papers published in Bioinorganic Chemistry and Applications and Bioorganic and Medicinal Chemistry, Professor Aoki said, “We looked at how we could cause a cancer cell to die and developed an artificial TRAIL (tumor necrosis factor related apoptosis inducing ligand) mimic that destroys cancer cells. In nature, TRAIL is a protein that binds to death receptors and induces programmed cell death, which is known as apoptosis.”
Researchers at the Aoki Lab synthesized iridium complex-peptide hybrid that can bind to death receptors, which induces programmed cell death such as TRAIL-like apoptosis or necrosis-like cell death of cancer cells. It is the first reported example in available literature of artificial luminescent TRAIL mimics that can induce either apoptosis or necrosis-type cell death. The wild type TRAIL binds with death receptors on cancer cells and causes only apoptosis. However, the TRAIL “mimics” synthesized by these researchers bind with the death receptors on cancer cells, and can cause both apoptosis and necrosis-type cell death. How the TRAIL mimics induce cell death via both processes is a mystery, and is the focus of research by Professor Aoki and colleagues.
“The fight against cancer is important because as people live longer, more and more people will be susceptible to cancer,” said Professor Aoki, “and one of the key challenges is going to be finding more efficient ways of collecting cancer cells for early diagnosis.”
The spread of cancer via blood is facilitated by circulating tumor cells (CTCs), which originate from primary cancer tissues. In a paper published in Biological and Pharmaceutical Bulletin, Professor Aoki, Professor at Faculty of Pharmaceutical Sciences at TUS, and his colleagues have described the combined use of a Particle Size Analyzer and computer software to distinguish cancer cells from normal cells, especially when cancer cells are similar in size to some of the normal white blood cells. In another related paper published in the ACS Biomaterials Science & Engineering, Professor Aoki and colleagues discuss how a simple technique using glass-bead filters (GBFs) can help collect, grow, and re-collect cancer cells.
With the understanding that cancer cells are larger in size than normal blood cells, the researchers developed a GBF-based filtration method that effectively sieves out the former. In this manner, a combination of chemical, material, biochemical, physical, and computational approaches can help improve the accuracy of cell-based diagnostic approaches for cancer.
The battle against cancer is being fought on multiple fronts. It is this multi-pronged attack that is helping scientists inch closer to cancer cure. The work of Professor Aoki and his team is a shot in the arm for such longstanding efforts to understand cancer with the aim of combating it.
Titles of original papers
- Size-Based Differentiation of Cancer and Normal Cells by a Particle Size Analyzer Assisted by a Cell-Recognition PC Software
Biological and Pharmaceutical Bulletin (DOI: 10.1248/bpb.b17–00776)
- Simple and Convenient Method for the Isolation, Culture, and Re-collection of Cancer Cells from Blood by Using Glass-Bead Filters
ACS Biomaterials Science and Engineering (DOI: 10.1021/acsbiomaterials.8b01335)
- Luminescent Iridium Complex-Peptide Hybrids (IPHs) for Therapeutics of Cancer: Design and Synthesis of IPHs for Detection of Cancer Cells and Induction of Their Necrosis-type Cell Death
Bioinorganic Chemistry and Applications (DOI: org/10.1155/2018/7578965)
- Design and synthesis of a luminescent iridium complex-peptide hybrid (IPH) that detects cancer cells and induces their apoptosis
Bioorganic and Medicinal Chemistry (DOI: 10.1016/j.bmc.2018.08.016)
About The Tokyo University of Science
Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japan’s development in science through inculcating the love for science in researchers, technicians, and educators.
With a mission of “Creating science and technology for the harmonious development of nature, human beings, and society”, TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today’s most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field. Website: https://www.tus.ac.jp/en/
About the author
Professor Shin Aoki is a Professor of cancer biology & research at the Faculty of Pharmaceutical Sciences, Tokyo University of Science. He is engaged in the study of medicinal chemistry, pharmacology, bioinorganic chemistry, and supramolecular chemistry. He is a recipient of the Award of Japan Society of Coordination Chemistry for Young Scientists (1999); the AJINOMOTO Award in Synthetic Organic Chemistry, Japan (2001); and the Pharmaceutical Society of Japan Award for Young Scientists (2002). He is a graduate from the University of Tokyo with B. S. (1986), M.S. (1988), and Ph.D. (1992) degrees in pharmaceutical sciences. He holds a post doctorate degree from the Department of Chemistry, the Scripps Research Institute, USA.