Published online Feb 24, 2024. doi: 10.5306/wjco.v15.i2.317
Peer-review started: October 9, 2023
First decision: November 23, 2023
Revised: December 6, 2023
Accepted: January 8, 2024
Article in press: January 8, 2024
Published online: February 24, 2024
Processing time: 133 Days and 17.4 Hours
Limonin is one of the most abundant active ingredients of Tetradium ruticarpum. It exerts antitumor effects on several kinds of cancer cells. However, whether limonin exerts antitumor effects on colorectal cancer (CRC) cells and cancer stem-like cells (CSCs), a subpopulation responsible for a poor prognosis, is unclear.
To evaluate the effects of limonin on CSCs derived from CRC cells.
CSCs were collected by culturing CRC cells in serum-free medium. The cytotoxicity of limonin against CSCs and parental cells (PCs) was determined by cholecystokinin octapeptide-8 assay. The effects of limonin on stemness were detected by measuring stemness hallmarks and sphere formation ability.
As expected, limonin exerted inhibitory effects on CRC cell behaviors, including cell proliferation, migration, invasion, colony formation and tumor formation in soft agar. A relatively low concentration of limonin decreased the expression stemness hallmarks, including Nanog and β-catenin, the proportion of aldehyde dehydrogenase 1-positive CSCs, and the sphere formation rate, indicating that limonin inhibits stemness without presenting cytotoxicity. Additionally, limonin treatment inhibited invasion and tumor formation in soft agar and in nude mice. Moreover, limonin treatment significantly inhibited the phosphorylation of STAT3 at Y705 but not S727 and did not affect total STAT3 expression. Inhibition of Nanog and β-catenin expression and sphere formation by limonin was obviously reversed by pretreatment with 2 μmol/L colievlin.
Taken together, these results indicate that limonin is a promising compound that targets CSCs and could be used to combat CRC recurrence and metastasis.
Core Tip: Colorectal cancer (CRC) is recognized worldwide as one of the most common malignancies and frequently leads to cancer-related death and the subpopulation termed cancer stem-like cell contributes critically to recurrence and metastasis. However, therapeutic molecule or strategy targeting to this subpopulation is still largely unknown. Here, we introduce Limonin, is one of the most abundant active ingredients of Tetradium ruticarpum, as a promising molecule targeting to cancer stem-like cells for CRC therapy.