Abstract
Evodiamine, an alkaloid contained in traditional Asian herbal medicines that have been used for hundreds years, is interesting due to its cytotoxic effects against many cancers. We examined the effect of evodiamine on the cancer stem cell (CSC) population and the bulk cultured cancer cells (BCC) of colon cancers to examine the double targeting effect. We found that three colon cancer cell lines’ BCC and CSC are effectively targeted by evodiamine. Evodiamine was able to suppress BCC proliferation and induce apoptosis of the cells captured in G2/M phase, as previously reported. However, evodiamine did not cause the accumulation of CSCs at a certain stage of the cell cycle, resulting in the elimination of stemness through an unknown mechanism. By analyzing the expression of 84 genes related to CSCs in two colon cancer cell lines’ CSC, as well as performing further informatics analyses, and quantitative RT-PCR analyses of 24 CSC genes, we found that evodiamine suppressed the expression of the genes that control key signaling pathways of CSC, namely, WNT and NOTCH signaling, to lead CSC elimination. These results suggest that evodiamine should be further developed for targeting both BCCs and CSCs in colon cancers.
Highlights
Over the last half century, intense efforts led by developed countries have been devoted to cancer research, many new anticancer therapeutic strategies were developed, and there have been significant improvements in the prognosis of several subtypes of cancer
We found that, in comparable concentrations, this compound modulates the p53-p21-Rb pathways only in breast cancer stem cell (CSC) but not in bulk cultured cancer cells (BCC) holding them at G1 stage [13], and we hypothesized that evodiamine may target the colon cancer cells
To examine if evodiamine could be used to treat the colon BCCs and CSCs together, we tested if evodiamine suppressed the growth of both the BCCs and CSCs of colon cancers using three colon cancer cell lines (HT29, SW480, and HCT15)
Summary
Over the last half century, intense efforts led by developed countries have been devoted to cancer research, many new anticancer therapeutic strategies were developed, and there have been significant improvements in the prognosis of several subtypes of cancer. Many therapeutic approaches, including radiation and chemotherapeutic agents, may even induce CSC number and the potentials [5,6,7] This CSC population may share many normal stem cell-like characteristics, and it is difficult. We tested the potential for evodiamine as a colon CSC-targeting agent and compared the effect in BCCs to determine if the compound can be used to eliminate both populations of colon cancer cells. Evodiamine was an effect targeting agents for both BCC and CSC inducing apoptotic cell deaths and reduced the stem cell potential in vitro and in vivo. Biochemical and genetic mechanistic study revealed WNT and Notch pathway, which are essential for cancer stem cell signaling, are primarily modulated by evodiamine in CSC of two cell lines suggesting evodiamine as a strong candidate to target colorectal BCCs and CSCs together
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