A composition of ursolic acid derivatives from Ludwigia hyssopifolia induces apoptosis in throat cancer cells via the Akt/mTOR and mitochondrial signaling pathways and by modulating endoplasmic reticulum stress

• Published in: Journal of ethnopharmacology Vol. 319; no. Pt 3; p. 117351
• Main Authors: Liu, Wenqi, Kang, Shiwen, Chen, Huijian, Bahetjan, Yerlan, Zhang, Jinyan, Lu, Rumei, Zheng, Ni, Yang, Guangzhong, Yang, Xinzhou
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 30.01.2024
• Subjects: Akt; Animals; Apoptosis; China; Endoplasmic reticulum stress; Humans; Ludwigia hyssopifolia; Mice; Mice, Nude; Mitochondrial apoptosis; mTOR; Neoplasms; Pharynx; Proto-Oncogene Proteins c-akt; Signal Transduction; Throat cancer; TOR Serine-Threonine Kinases; Ursolic Acid; China; mTOR; Mitochondrial apoptosis; Akt; Throat cancer; Ludwigia hyssopifolia; Endoplasmic reticulum stress
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2023.117351

Ludwigia hyssopifolia (LH), an ethnopharmacological herb used in Guangxi Zhuang medicine, is known for its extensive therapeutic use in treating throat disorders. The anti–laryngeal-cancer benefits of the ethyl acetate and petroleum ether fractions of the ethanolic extracts of LH have been shown in our prior cell-based research. Nevertheless, the specific impacts and underlying processes by which LH combats throat cancer effects have not been fully understood. This study involved the extraction of a composition containing two derivatives of ursolic acid from LH (LH-CUAD). The present study aimed to assess the anti-throat-cancer effects of these derivatives and the underlying mechanisms through in vitro and in vivo experiments. Solvent extraction, fractionation, chromatography, and semipreparative high-performance liquid chromatography were used for the extraction, purification, and analysis of LH-CUAD. The in vitro and in vivo anti–throat-cancer effects of LH-CUAD were investigated using the throat cancer cell lines Hep-2 and FaDu as well as Hep-2 tumor–bearing nude mice. LH-CUAD significantly inhibited the proliferation and migration of throat cancer cells without any prominent toxicity. The Hoechst 33258 staining, Annexin V-FITC/PI double-staining assays, and flow cytometry confirmed that LH-CUAD could induce throat cancer cell death from early to late apoptosis in vitro. LH-CUAD exhibited significant antitumor activity and low toxicity in a xenograft model, and induced throat cancer cells apoptosis in vivo. The apoptotic effects of LH-CUAD therapy were validated using Western blotting, which demonstrated the activation of a caspase cascade response triggered by an imbalance between the endoplasmic reticulum and mitochondria. In addition, it was observed that LH-CUAD exhibited inhibitory effects on AKT and mTOR phosphorylation, hence promoting apoptosis. LH-CUAD induces apoptosis in both in vivo and in vitro models of throat cancer. This effect is achieved by activating the mitochondrial pathway, inhibiting the AKT/mTOR pathway and initiating endoplasmic reticulum stress. The findings of this study suggest that LH-CUAD has the potential to offer a novel approach to the clinical management of throat cancer. [Display omitted] •Ludwigia hyssopifolia is a herb used in Guangxi Zhuang medicine to treat disorders of throat.•A composition containing two ursolic acid derivatives from Ludwigia hyssopifolia (LH-CUAD) could effectively inhibit the proliferation and migration of throat cancer cells.•LH-CUAD could exhibit significant antitumor activity and low toxicity in a xenograft model.•LH-CUAD could induce apoptosis through the suppression of AKT and mTOR phosphorylation and the imbalance in the mitochondria and endoplasmic reticulum.•We first reported the molecular mechanism of LH-CUAD against throat cancer in vivo and in vitro.