Buddlejasaponin IV induces apoptotic cell death by activating the mitochondrial‑dependent apoptotic pathway and reducing α<sub>2</sub>β<sub>1</sub> integrin‑mediated adhesion in HT‑29 human colorectal cancer cells

Kim,Jin-Eun; Lee,Sun Kyoung; Park,Junhee; Jung,Min Ju; An,So-Eun; Yang,Hye Ji; Chung,Won-Yoon

doi:10.3892/or.2023.8495

March-2023 Volume 49 Issue 3

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March-2023 Volume 49 Issue 3

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Article

Buddlejasaponin IV induces apoptotic cell death by activating the mitochondrial‑dependent apoptotic pathway and reducing α₂β₁ integrin‑mediated adhesion in HT‑29 human colorectal cancer cells

Authors:
- Jin-Eun Kim
- Sun Kyoung Lee
- Junhee Park
- Min Ju Jung
- So-Eun An
- Hye Ji Yang
- Won-Yoon Chung
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Affiliations: Department of Oral Biology, Oral Cancer Research Institute, and BK21 FOUR Project INNO‑Dent Convergence Academy, Yonsei University College of Dentistry, Seoul 03722, Republic of Korea
Article Number: 58
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Published online on: February 10, 2023

https://doi.org/10.3892/or.2023.8495
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Abstract

Colon cancer is one of the most frequent malignant neoplasms worldwide. Epidemiological studies suggested that the development of colon cancer can be prevented by plant‑derived ingredients. In the present study, the chemopreventive activity of buddlejasaponin IV (BS‑IV), isolated from the aerial part of Pleurospermum kamtschaticum, was investigated using cell viability, DNA fragmentation, caspase‑3 activity, anoikis, cell adhesion, and flow cytometry assays and a murine lung metastasis model. Protein expression levels were detected by western blotting. Treatment with BS‑IV significantly reduced cell viability and caused DNA fragmentation in HT‑29 human colorectal cancer cells. BS‑IV increased the ratio of Bax to Bcl‑2 by significantly inhibiting Bcl‑2 expression levels. BS‑IV reduced expression levels of procaspase‑9, procaspase‑3, and full‑length poly (ADP‑ribose) polymerase (PARP) and increased cleaved PARP and nonsteroidal anti‑inflammatory drug activated gene‑1 expression levels and caspase‑3 activity. In addition, BS‑IV decreased the attachment of HT‑29 cells to the extracellular matrix proteins collagen type I and IV and downregulated cell surface expression of α₂β₁ integrin by inhibiting its glycosylation. BS‑IV also reduced the expression and phosphorylation levels of focal adhesion kinase (FAK) and Akt, and the reduced FAK and Akt levels were rescued by treatment with a caspase‑3 inhibitor Z‑VAD‑FMK. Furthermore, orally administered BS‑IV inhibited the formation of tumor nodules in Balb/C mice intravenously injected with CT‑26 murine colorectal cancer cells. Collectively, these findings indicated that BS‑IV induces apoptosis via the mitochondrial‑dependent pathway by increasing the ratio of Bax to Bcl‑2 and activating caspases. BS‑IV also induces anoikis by inhibiting α₂β₁ integrin‑mediated cell adhesion and signaling and inhibits the lung metastasis of colon cancer cells. Therefore, BS‑IV may serve as a promising cancer chemopreventive agent.

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