2-O-Methylmagnolol Induces Apoptosis and Inhibits IL-6/STAT3 Signaling in Oral Squamous Cell Carcinoma

Abstract

Background/Aims: 2-O-methylmagnolol (MM1), a derivative of magnolol bearing one methoxy moiety, has been shown to display improved anti-tumor activity against skin cancers. In this study, we examined the anti-tumor effects of magnolol and MM1 on oral squamous cell carcinoma (OSCC). Methods: Trypane blue staining and clonogenic assays were performed to determine the cytotoxic effects of magnolol and MM1 in OSCC cells. Migration and matrigel invasion assays were carried out to examine the metastasis effects of magnolol and MM1 in OSCC cells. IL6-stimulation, Western blot, and immunohistochemistry were used to investigate the IL-6/STAT3 signaling and apoptosis. A bioluminescent mouse model of orthotopically implanted SAS cells was used to determine the anti-tumor activity of MM1 in vivo. Results: MM1 displays greater activity than magnolol on affecting the cytotoxicity, migration, and invasion of OSCC cells cultured in vitro. The improved anti-tumor activity of MM1 was shown to associate with its greater activity to inhibit STAT3 signaling and to induce apoptosis in the OSCC. In addition, we presented evidence that MM1 is effective in inhibiting the growth of orthotopic implanted OSCC cells in vivo. Conclusion: Our data indicate that MM1 displays greater anti-tumor activity than magnolol in OSCC and is an attractive agent to be further explored for its potential clinical application.

2-O-Methylmagnolol, a Magnolol Derivative, Suppresses Hepatocellular Carcinoma Progression via Inhibiting Class I Histone Deacetylase Expression

“…However, MM1 displayed a significantly stronger inhibitory effect on cell growth than magnolol at similar concentrations, indicating a greater tumor-suppressive activity than that of magnolol ( Figures 1C-F). The half-maximal inhibitory concentration (IC 50 ) of magnolol toward Huh7 and HepG2 cells was ∼97 and 65 µM, respectively, which is similar to results from other studies (46)(47)(48), while the IC 50 of MM1 in Huh7 and HepG2 cells was 48 and 61 µM, respectively. Moreover, only a slight inhibitory effect was observed on the growth of the HFB cell line at the highest concentrations of magnolol and MM1 ( Figure 1B).…”

Potential roles and molecular mechanisms of phytochemicals against cancer

“…37 It also inhibits the IL-6/STAT3 signaling pathway to induce cell apoptosis in oral squamous cell carcinoma. 38…”

“…Phytochemicals, with natural plants being their potential sources and which include flavonoids, polyphenols, terpenoids, alkaloids, saponins, coumarins and so on, could target diverse signaling pathways, which may be a favorable way to block cancer progression and chemotherapy drug resistance. 15–38…”

Impact of Interleukin-6 on Oral Squamous Cell Carcinoma Among the South Indian Population

“…In terms of systemic malignant tumors based on frequency, head and neck cancer ranks the sixth most common malignancy with reference to frequency and occurrence, with around 90% of the cases being OSCC with poor prognosis. However, it is unclear how OSCC develops [ 11 ]. On the one hand, persistent inflammation can draw inflammatory and immune cells to the tumor tissue, and as the tumor grows, these growth roles shift from immune monitoring and suppression to stimulating the growth of tumor cells.…”