MicroRNAs Contribute to the Anticancer Effect of 1'-Acetoxychavicol Acetate in Human Head and Neck Squamous Cell Carcinoma Cell Line HN4

Abstract

1'-Acetoxychavicol acetate (ACA), extracted from rhizomes of tropical ginger, possesses antitumor properties against a wide variety of malignancies. MicroRNAs have been found to act as oncogenes and as tumor suppressor genes in the development of cancer. The purpose of this study was to investigate the miRNA involved in the molecular mechanisms of ACA action on tumor inhibition. It was found that ACA significantly inhibited the growth of human head and neck squamous cell carcinoma cell line HN4 and induced cell apoptosis. Further studies indicated that ACA downregulated the expression of miR-23a in HN4 cells. Transfection with anti-miR-23a inhibited the proliferation of HN4 cells and induced cell apoptosis. In addition, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was confirmed to be the target of miR-23a. Taken together, our findings suggest that ACA might have anticancer effects against human head and neck cancer through downregulation of miR-23a, which can repress tumor suppressor PTEN.

microRNA-23a in Human Cancer: Its Roles, Mechanisms and Therapeutic Relevance

“…Other reported targets of the miR-23a to promote cancer cell proliferation, while suppressing cellular apoptosis, include phosphatase and tensin homolog (PTEN) [81], special AT-Rich Sequence Binding Protein 1 (SATB1) [17], Fas [39], protein Phosphatase 2 Regulatory Subunit B’Epsilon (PPP2R5E), and Raf kinase inhibitor protein (RKIP) [8].…”

“…Regulation of the miR-23a expression by a particular transcriptional factor could be significantly deviated in different types of cancer. For example, p65 NF-κB can strongly bind to the promoter region of the miR-23a-27a-24 cluster and up-regulate the miR-23a expression in the erythroleukaemia cells [125], and an NF-κB inhibitor 1′-Acetoxychavicol acetate could significantly down-regulate the expression of the miR-23a in the head and neck squamous cell carcinoma cells [81]. However, the p65 NF-κB subunit could be a transcriptional repressor of the miR-23a, in leukemic Jurkat cells.…”

Current state of phenolic and terpenoidal dietary factors and natural products as non-coding RNA/microRNA modulators for improved cancer therapy and prevention

“…More precisely, the tumor suppressor miRNAs miR-138, miR-210 and miR-744 were upregulated by 1′-acetoxychavicol acetate in combination with cisplatin [251] . In addition, oncogenic miR-23a was suppressed in head-and-neck squamous cells (HN4) associated with PTEN upregulation and increased apoptosis induction after treatment with 1′-acetoxychavicol acetate [252] .…”

Regulation of MicroRNAs by Natural Agents: New Strategies in Cancer Therapies

“…These include miR-138, miR-210, and miR-744 with their predicted targets involved in signalling pathways regulating apoptosis and cell cycle progression [ 37 ]. Another study reported that ACA also downregulated miR-23a in HN4 head and neck squamous cells and its inhibition suppressed cell proliferation and induced apoptosis, with PTEN confirmed as its target [ 121 ]. Sulforaphane, an isothiocyanate derived from cruciferous vegetables such as broccoli and broccoli sprouts, upregulated 15 miRNAs (miR-372, miR-342-3p, miR-486-5p, miR-9, miR-9∗, miR-145, miR-146a, miR-629, miR-505, miR-758, miR-30a∗, miR-27b∗, miR-135b∗, miR-27b, and miR-23b) and downregulated 3 miRNAs (miR-633, miR-155, and miR-106a∗) in NCM460 and NCM356 normal colon epithelial cells [ 122 ].…”