A rearranged abietane diterpenoid from Clerodendrum mandarinorum inhibits tumor progression of oral squamous cell carcinoma in vitro

Abstract

Tongue cancer, a prevalent form of oral malignancy, particularly manifests as tongue squamous cell carcinoma (TSCC), which holds the highest incidence among oral squamous cell carcinoma cases, representing 43.4 % of occurrences. Presently, surgical resection stands as the primary treatment for TSCC, with no effective pharmaceutical interventions identified. This study aims to search for the potential anti-tumor properties and molecular mechanisms of a rearranged abietane diterpenoid extracted from Clerodendrum mandarinorum. Within this investigation, six known rearranged abietane diterpenoids (1–6) were isolated and characterized from C. mandarinorum. Notably, compound 1 demonstrated the most robust inhibitory effect against CAL-27 cells. Pharmacological assays further substantiated that compound 1 significantly restrained the proliferation, migration, and invasion of CAL-27 cells. Moreover, it was revealed that compound 1 directly interacted with TGFβR2, a pivotal receptor in the downstream signaling pathways of TGF-β/Smad and PI3K/AKT. Transcriptome analysis provided additional confirmation of these observations. Overall, our study highlights the promising potential of compound 1 as a therapeutic agent for the treatment of oral squamous cell carcinoma.

Keywords

• Clerodendrum mandarinorum
• Rearranged abietane diterpenoids
• Tongue squamous cell carcinoma
• Transforming Growth Factor Beta Receptor 2 (TGFβR2)
• Epithelial-mesenchymal transition (EMT)