Ononin Shows Anticancer Activity Against Laryngeal Cancer via the Inhibition of ERK/JNK/p38 Signaling Pathway

Abstract

BackgroundLaryngeal cancer is a type of head and neck tumor with a poor prognosis and survival rate. The new cases of laryngeal cancer increased rapidly with a higher mortality rate around the world.ObjectiveThe current research work was focused to unveil the in vitro antitumor effects of ononin against the laryngeal cancer Hep-2 cells.MethodologyThe cytotoxic effects of ononin against the laryngeal cancer Hep-2 cells and normal HuLa-PC laryngeal cells were studied using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The intracellular Reactive Oxygen Species (ROS) generation, apoptotic cell death, Mitochondrial Membrane Potential (MMP), and cell adhesion on the 25 and 50 µM ononin-treated Hep-2 cells were detected using respective staining assays. The levels of TBARS and antioxidants were assayed using specific kits. The expressions of c-Jun N-terminal kinase 1/2 (JNK1/2), Extracellular Signal-regulated Kinase 1/2 (ERK1/2), p38, Phosphatidylinositol-3 Kinase 1/2 (PI3K1/2), and protein kinase-B (Akt) in the ononin-treated Hep-2 cells were investigated using Reverse Transcription-Polymerase Chain Reaction (RT-PCR) assay.ResultsThe ononin treatment effectively inhibited the Hep-2 cell viability but did not affect the viability of HuLa-PC cells. Furthermore, the ononin treatment effectively improved the intracellular ROS accumulation, depleted the MMP, and triggered apoptosis in Hep-2 cells. The Thiobarbituric acid reactive substances (TBARS) were improved, and Glutathione (GSH) levels and Superoxide dismutase (SOD) were depleted in the ononin-administered Hep-2 cells. The ononin treatment substantially inhibited the JNK/ERK/p38 axis in the Hep-2 cells.ConclusionTogether, the outcomes of this exploration proved that the ononin has remarkable antitumor activity against laryngeal cancer Hep-2 cells.

Danggui Buxue Tang potentiates the cytotoxicity of 5‐fluorouracil on colorectal adenocarcinoma cells: A signaling mediated by c‐Jun N‐terminal kinase

“…In addition, ononin, an active chemical in DBT, demonstrated antitumorigenic properties. This result was consistent in accordance with Ye et al (2022), who reported that ononin treatment significantly inhibited the Hep-2 cell viability and JNK/ERK/p38 axis, resulting in a remarkable antitumor effect. Hence these findings suggest that ononin in DBT synergizes with a chemotherapeutic drug to promote anti-CRC cell proliferation.…”

“…From the MTT data, we found only ononin presented at 1 μM was capable of inhibiting HT‐29 cell viability (Figure 9b). In fact, ononin was found to possess antiangiogenic properties and to inhibit the proliferation of different cancer cells both in vitro and in vivo (G. Gong & Zheng, 2021; Gu et al, 2021; Ye et al, 2022). Here, we demonstrated colony formation and anti‐tumor cell proliferation on cultured HT‐29 cells (Figure 9b–e).…”

“…Furthermore, the co-treatment of AR with a chemotherapeutic drug alleviated cancer symptoms and enhanced patients' quality of life (Bamodu et al, 2019). DBT contains significant amounts of ononin, which has been reported to possess anti-cancer activities inhibiting the proliferation of laryngeal cancer in cell and animal models (Ye et al, 2022). After the co-treatment of 5-FU and DBT in cultured HT-29 cells, the reduction of cell survival was up to 50%, suggesting that DBT might enhance the effectiveness of 5-FU.…”

Anti-Invasive and Anti-Migratory Effects of Ononin on Human Osteosarcoma Cells by Limiting the MMP2/9 and EGFR-Erk1/2 Pathway

“…Metastasis is the main cause of clinical manifestations; however, the underlying mechanisms involved in metastasis and chemoresistance in the development of osteosarcoma remain unclear. Ononin is an active principle mostly found in fruits and vegetables that possesses several biological activities including anticancer properties [26]. Currently, no comprehensive study has been conducted on ononin and osteosarcoma.…”

Antitumor Effects of Ononin by Modulation of Apoptosis in Non-Small-Cell Lung Cancer through Inhibiting PI3K/Akt/mTOR Pathway

“…The extensive role and the related synergistic mechanisms of AR with cisplatin on laryngeal squamous cell carcinoma have also been well established [ 37 ]. Ononin is an active principle primarily found in AR that possesses various pharmacological properties including anticancer activities [ 38 ]. To date, there is no study related to the synergistic effects of ononin and PTX.…”