Geniposide inhibits cell proliferation and migration in human oral squamous carcinoma cells via AMPK and JNK signaling pathways

Bai,Guohui; Chen,Bin; Xiao,Xin; Li,Yuexin; Liu,Xia; Zhao,Dan; Zhang,Lei; Zhao,Degang

doi:10.3892/etm.2022.11642

Geniposide inhibits cell proliferation and migration in human oral squamous carcinoma cells via AMPK and JNK signaling pathways

Authors:
- Guohui Bai
- Bin Chen
- Xin Xiao
- Yuexin Li
- Xia Liu
- Dan Zhao
- Lei Zhang
- Degang Zhao
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Affiliations: Department of Oral Medicine, Hospital of Stomatology, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China, Zunyi Engineering Technology Research Center of Physical and Chemical Analysis, Institute of Life Sciences, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China, Key Laboratory of Plant Resources Conservation and Germplasm Innovation in Mountainous Region (Ministry of Education), Institute of Agro‑Bioengineering and College of Life Sciences, Guizhou University, Guiyang, Guizhou 550025, P.R. China, Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China
Published online on: October 4, 2022 https://doi.org/10.3892/etm.2022.11642
Article Number: 706
Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Iridoids are a special class of cyclopentanoid monoterpenes, which exhibit a wide range of biological effects. The present study aimed to investigate the potential effects of three iridoids genipin, geniposide and geniposidic acid on three human oral squamous cell carcinoma (OSCC) cell lines HSC‑2, SCC‑9 and A253 in addition to studying the possible underlying mechanisms. Cell viability assay revealed that geniposide treatment significantly suppressed the proliferation of all three cancer cell lines. In addition, geniposide induced SCC‑9 cell cycle arrest at the G2/M phase (flow cytometry) through downregulation of cyclin‑dependent kinase 2 and Cyclin A2 expression (western blot analysis), whilst also inducing cell apoptosis (flow cytometry and acridine orange/ethidium bromide staining) by dissipating the mitochondrial membrane potential (flow cytometry), and upregulating the expression of cleaved caspase‑3 and cleaved poly‑ADP ribose polymerase (western blot analysis). A wound‑healing assay indicated that geniposide impaired SCC‑9 cell migration by increasing the expression of E‑cadherin (western blot analysis), whilst suppressing the expression of MMP‑2 (western blot analysis). Western blot analysis also demonstrated that geniposide induced autophagy in SCC‑9 cells by upregulating the expression of Beclin‑1 and light chain 3‑II. Mechanistically, geniposide activated the 5'‑AMP‑activated protein kinase signaling pathway and inhibited the JNK signaling pathway in SCC‑9 cells (western blot analysis). The present results indicated that geniposide is able to inhibit the proliferation and migration of the tongue squamous carcinoma cell line SCC‑9, suggesting a potential strategy for OSCC treatment.

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