Abstract
Background: Colorectal cancer (CRC) is one of the diseases with high prevalence and mortality worldwide. In particular, metastatic CRC shows low probability of surgery and lacks proper treatment. In this study, we conducted experiments to investigate the inhibitory effect of betulin against metastatic CRC and related mechanisms. Methods: Water-soluble tetrazolium assay was used to determine the effect of betulin on metastatic CRC cell viability. Flow cytometry and TUNEL assay were performed to confirm whether betulin can induce apoptosis, autophagy, and cell cycle arrest. A lung metastasis mouse model was employed to estimate the anti-metastatic effect of betulin. Results: betulin decreased viability of metastatic CRC cells, including CT26, HCT116, and SW620 cell lines. Through PI3K/Akt/mTOR inactivation, betulin induced AMPK-mediated G0/G1 phase arrest and autophagy of CT26 and HCT116 cells. In addition, betulin occurred caspase-dependent apoptosis via the mitogen-activated protein kinase signaling pathway in metastatic CRC cells. Moreover, orally administered betulin significantly inhibited metastasis of CT26 cells to the lung. Conclusion: Our results demonstrate the anti-metastatic effect and therapeutic potential of betulin in metastatic CRC treatment.
Highlights
Colorectal cancer (CRC) is the second leading cause of death in the Western world in both males and females [1]
Real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) results showed that betulin treatment significantly decreased mRNA expressions of cyclin D1 and CDK4 in both CT26 and HCT116 cells (Figure 2e,f)
Since we is mainly mediated via the PI3K/Akt/mTOR and AMPK/mTOR signaling observed activation and changes in cell viability by betulin, we investigated whether betulin
Summary
Colorectal cancer (CRC) is the second leading cause of death in the Western world in both males and females [1]. Induction of cell cycle arrest and programmed cell death in cancer cells are efficient strategies in cancer treatment. There are two types of programmed cell death, apoptosis and autophagy. Apoptosis (type I programmed cell death) has several morphological and biochemical change characteristics, such as cell shrinkage, membrane blebbing, nuclear condensation, and DNA fragmentation [5]. Methods: Water-soluble tetrazolium assay was used to determine the effect of betulin on metastatic CRC cell viability. Flow cytometry and TUNEL assay were performed to confirm whether betulin can induce apoptosis, autophagy, and cell cycle arrest. A lung metastasis mouse model was employed to estimate the anti-metastatic effect of betulin
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