University of the Philippines (UP) chemists have synthesized novel hybrid molecules that show promise in fighting cancer by limiting the spread of aggressive breast cancer cells.
The compounds, called lithocholic acid-3,3′-diindolylmethane (LCA-DIM) hybrids, work by inhibiting the enzyme sialyltransferase (ST), which is key to a process that allows cancer cells to hide from the immune system and promote progression.
The study, led by chemists Christian Angelo Concio and Dr. Susan Arco of the University of the Philippines – Diliman College of Science’s Institute of Chemistry (UPD-CS IC) in collaboration with Dr. Wen-Shan Li’s group in Taiwan, found that the LCA-DIM hybrids were effective in inhibiting the spread of different triple-negative breast cancer (TNBC) cell lines. TNBC is an aggressive and hard-to-treat cancer type.
Christian Angelo Concio, chemist at the UPD-CS IC, said that unlike traditional anticancer drugs like doxorubicin, which directly kill cancer cells but often have severe side effects and lead to resistance, their ST inhibitor targets cancer metastasis.
“It targets cancer metastasis, aiming to block the spread of cancer cells rather than just destroy them, thereby helping to slow disease progression and make cancer treatment more manageable,” he said.
The hybrids specifically targeted the ST6GAL1 enzyme, showing high selectivity compared to the ST3GAL1 enzyme.
This selectivity is considered ideal for next-generation ST inhibitors, as different STs are overexpressed in specific cancer types. Inhibiting ST prevents hypersialylation, a process where cancer cells coat their surface with excessive sialic acid to avoid the immune system.
The research was inspired by the chemists’ previous work on indoles—compounds known for their stability and potential anticancer properties. They hypothesized that combining the indole-rich diindolylmethane (DIM) with lithocholic acid (LCA), a known ST inhibitor scaffold, would enhance its inhibitory effect, which proved correct.
In response to the growing cancer burden in the Philippines, where over 180,000 new cases are diagnosed annually and cancer is estimated to cause over 300 Filipino deaths daily, the research is a crucial step in innovation.
The International Agency for Research on Cancer (IARC) recorded nearly 189,000 new cancer cases and more than 113,000 cancer-related deaths in the Philippines in 2022. Globally, new cases are projected to rise by 77 percent to over 35 million by 2050, from 2022 figures.
While the study focused on breast cancer cells, Concio intends to explore this approach in other cancers that also exhibit high levels of the ST6GAL1 enzyme, such as pancreatic and ovarian cancers.
The next steps include testing the hybrids for safety, stability and effectiveness in animal models to bring the research closer to real-world applications.
Their research paper, titled “Novel lithocholic acid-diindolylmethane hybrids as potent sialyltransferase inhibitors targeting triple-negative breast cancer: a molecular hybridization approach,” was published in RSC Medicinal Chemistry
