Molecular Mechanisms of Anticarcinogenic Potential of Hydrocotyle umbellata and Its Major Components

Abstract

Despite the development of several anticancer treatments, there remains a need for new drugs that can overcome resistance and reduce side effects. While the medicinal herb Hydrocotyle umbellata (H. umbellata) has been used to relieve pain and inflammation, its antitumor properties have not yet been explored. In this study, we investigated the anticarcinogenic potential of H. umbellata extract (HUE) and its major components, as well as the underlying molecular mechanisms. Our results showed that HUE inhibited the growth of various tumor cell lines, including B16F10, without affecting non-cancer cells. Furthermore, HUE was effective in treating and preventing tumor growth in mice. Our mechanistic studies revealed that HUE inhibited cellular respiration, thereby reducing tumor cell proliferation. When combined with 2-deoxy-D-glucose, HUE demonstrated an enhanced anticancer effect by increasing the rate apoptosis. Analysis of the ethyl acetate and n-butanol fractions of HUE identified 1,3,4-trihydroxy-2-butanyl-α-d-glucopyranoside and caffeoylquinic acid derivatives as the major components responsible for the observed anticancer effects. In conclusion, our findings suggest that HUE and its two major components have the potential to be developed as effective therapeutic agents for a wide range of tumors by targeting cancer cell metabolism.

Authors’ Contribution

JK: Investigation, Writing—Original Draft. SHP: Investigation, Writing—Original Draft. DYK: Methodology. HWR: Methodology, Supervision. HSJ: Conceptualization, Methodology, Supervision, Funding acquisition.

Disclosure Statement

The authors declare no conflict of interest and no financial interest.

Data Availability Statement

All datasets generated for this study are included in the article. Further inquiries can be directed to the corresponding author.

Additional information

Funding

This work was supported by the ITRC (Information Technology Research Center) support program supervised by the IITP (Institute for Information and Communications Technology Planning and Evaluation) and funded by the Ministry of Science and ICT (MSIT), Korea (IITP-2024-RS-2023-00258971). Additional support was provided by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (2021R1I1A3056109).