Effect of the Extracts from the Leaves and Branches of Sageretia thea on β-catenin Proteasomal Degradation in Human Colorectal and Lung Cancer Cells

상동나무(Sageretia thea) 잎과 가지추출물의 대장암과 폐암세포의 β-catenin 분해 유도 활성

Abstract

In this study, we evaluated the effect of branch (STB) and leave (STL) extracts from Sageretia thea on ${\beta}-catenin$ level in human colorecal cancer cells, SW480 and lung cancer cells, A549. STB and STL dose-dependently suppressed the growth of SW480 and A549 cells. STB and STL decreased ${\beta}-catenin$ level in both protein and mRNA level. MG132 decreased the downregulation of ${\beta}-catenin$ protein level induced by STB and STL. However, the inhibition of $GSK3{\beta}$ by LiCl or ROS scavenging by NAC did not block the reduction of ${\beta}-catenin$ protein by STB and STL. Our results suggested that STB and STL may downregulate ${\beta}-catenin$ protein level independent on $GSK3{\beta}$ and ROS. Based on these findings, STB and STL may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer and lung cancer.

이상의 연구 결과로 미루어 볼 때, 상동나무 가지 (STB)와 잎(STL)은 $GSK3{\beta}$와 ROS에 의존하지 않는 ${\beta}-catenin$의 분해 유도를 통해 대장암 및 폐암세포의 생육을 억제하는 것으로 나타났다. 본 결과는 상동나무 가지와 잎의 항암을 위한 대체보완소재 및 천연 항암제 개발을 위한 소재로 활용이 가능할 것으로 판단된다. 그러나 추가적 연구를 통해 상동나무 가지와 잎의 ${\beta}-catenin$의 분해 유도 관련 기전연구와 항암 활성물질의 분석연구가 필요할 것으로 사료된다.

Fig. 1. Effect of STB and STL on the cell growth in SW480 and A549 cells. (A and B) Cell growth was evaluated by MTT assay at 24 h after STB and STL treatment. *p < 0.05 compared to cell without STB and STB.

Fig. 2. Effect of STB and STB on β-catenin expression in SW480 and A549 cells. (A and B) A549 and SW480 cells were treated with STB and STL at the indicated concentrations for 24 h. Western blot and RT-PCR analysis was performed against β-catenin. Actin and GAPDH were used as internal controls for Western blot and RT-PCR, respectively. *p < 0.05 compared to cell without STB and STL.

Fig. 3. Effect of STB and STL on β-catenin proteasomal degradation in SW480 and A549 cells. (A and B) SW480 and A549 cells were pretreat with 20 μM of MG132 for 2 h and then co-treated with STB and STL for 12 h. Western blot analysis was performed against β- catenin. Actin was used as an internal control. *p < 0.05 compared to cell without STB and STL.

Fig. 4. Effect of GSK3β or ROS on β-catenin proteasomal degradation induced by STB and STL in SW480 and A549 cells. (A and B) SW480 and A549 cells were pretreated with 20 mM of LiCl or 10 mM of NAC for 2 h and then co-treated with STB and STL for 12 h. After the treatment, Western blot analysis was performed against β-catenin. Actin was used as internal control. *p < 0.05 compared to cell without STB and STL.

Table 1. Sequence of oligonucleotide primers used for RT-PCR