Suppressive effect of α-mangostin for cancer stem cells in colorectal cancer via the Notch pathway

Min Kyoung Jo, Chang Mo Moon, Eun Ju Kim, Ji Hee Kwon, Xiang Fei, Seong Eun Kim, Sung Ae Jung, Minsuk Kim, Yeung Chul Mun, Young Ho Ahn, Seung Yong Seo, Tae Il Kim

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Abstract

Background: Since colon cancer stem cells (CSCs) play an important role in chemoresistance and in tumor recurrence and metastasis, targeting of CSCs has emerged as a sophisticated strategy for cancer therapy. α-mangostin (αM) has been confirmed to have antiproliferative and apoptotic effects on cancer cells. This study aimed to evaluate the selective inhibition of αM on CSCs in colorectal cancer (CRC) and the suppressive effect on 5-fluorouracil (5-FU)-induced CSCs. Methods: The cell viability assay was performed to determine the optimal concentration of αM. A sphere forming assay and flow cytometry with CSC markers were carried out to evaluate the αM-mediated inhibition of CSCs. Western blot analysis and quantitative real-time PCR were performed to investigate the effects of αM on the Notch signaling pathway and colon CSCs. The in vivo anticancer efficacy of αM in combination with 5-FU was investigated using a xenograft mouse model. Results: αM inhibited the cell viability and reduced the number of spheres in HT29 and SW620 cells. αM treatment decreased CSCs and suppressed the 5-FU-induced an increase in CSCs on flow cytometry. αM markedly suppressed Notch1, NICD1, and Hes1 in the Notch signaling pathway in a time- and dose-dependent manner. Moreover, αM attenuated CSC markers CD44 and CD133, in a manner similar to that upon DAPT treatment, in HT29 cells. In xenograft mice, the tumor and CSC makers were suppressed in the αM group and in the αM group with 5-FU treatment. Conclusion: This study shows that low-dose αM inhibits CSCs in CRC and suppresses 5-FU–induced augmentation of CSCs via the Notch signaling pathway.

Original languageEnglish
Article number341
JournalBMC Cancer
Volume22
Issue number1
DOIs
StatePublished - Dec 2022

Keywords

  • Cancer stem cell
  • Colorectal cancer
  • Notch signal
  • Phytochemical agent
  • α-Mangostin

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