A Flavone Constituent from Myoporum bontioides Induces M-Phase Cell Cycle Arrest of MCF-7 Breast Cancer Cells

Abstract

Myoporum bontioides is a traditional medicinal plant in Asia with various biological activities, including anti-inflammatory and anti-bacterial characteristics. To identify the bioactive constituents from M. bontioides, a newly-identified flavone, 3,4′-dimethoxy-3′,5,7-trihydroxyflavone (compound 1), along with eight known compounds, were investigated in human MCF-7 breast cancer, SCC4 oral cancer, and THP-1 monocytic leukemia cells. Among these compounds, compound 1 exhibited the strongest antiproliferative activity with half-maximal inhibitory concentration (IC50) values ranging from 3.3 μM (MCF-7) to 8.6 μM (SCC4). Flow cytometric analysis indicated that compound 1 induced G2/M cell cycle arrest in MCF-7 cells. Mechanistic evidence suggests that the G2/M arrest could be attributable to compound 1’s modulatory effects on the phosphorylation and expression of numerous key signaling effectors, including cell division cycle 2 (CDC2), CDC25C, and p53. Notably, compound 1 downregulated the expression of histone deacetylase 2 (HDAC2) and HDAC4, leading to increased histone H3 acetylation and p21 upregulation. Together, these findings suggest the translational potential of compound 1 as a breast cancer treatment.

Long noncoding RNA MALAT1 regulates HDAC4‐mediated proliferation and apoptosis via decoying of miR‐140‐5p in osteosarcoma cells

“…Histone deacetylase 4 (HDAC4) plays global roles in the regulation of gene transcription, cell growth, survival and proliferation, and their aberrant expressions or activities contribute to cancer development . Zeng LS revealed that upregulated HDAC4 is associated with higher tumor grade, advanced clinical stage, and poor survival rate in esophageal carcinoma, also they found that HDAC4 promoted proliferation and G1/S cell cycle progression in EC cells .…”

“…Histone deacetylase 4 (HDAC4) plays global roles in the regulation of gene transcription, cell growth, survival and proliferation, and their aberrant expressions or activities contribute to cancer development. [5][6][7][8][9][10] Zeng LS revealed that upregulated HDAC4 is associated with higher tumor grade, advanced clinical stage, and poor survival rate in esophageal carcinoma, also they found that HDAC4 promoted proliferation and G1/S cell cycle progression in EC cells. 11 Vallabhapurapu | 4585 SUN aNd QIN SD demonstrated that HDAC4 and its downstream complex maintained repressive chromatin around pro-apoptotic genes Bim and BMF and regulates multiple myeloma (MM) survival and growth.…”

Anti-MRSA Sesquiterpenes from the Semi-Mangrove Plant Myoporum bontioides A. Gray

“…It grows above the tide lines by the sea and adapts to saline-alkali sand and rocky land, which plays an important role in wind-breaking and sand-fixation, as well as greening the environment [ 23 ]. In China, M. bontioides has been used as a folk medicine for antidermatosis, antipyretic, and antipsychotic [ 24 , 25 , 26 , 27 ]. Previous phytochemical studies have revealed some structurally diverse chemicals from this plant, including sesquiterpenoids, iridoids, monoterpenes, phenylethanoids, and flavonoids, some of which showed important bioactivities [ 28 , 29 , 30 , 31 , 32 , 33 ].…”

Chemical compositions and bioefficacy against Spodoptera litura of essential oil and ethyl acetate fraction from Myoporum bontioides leaves

“…This compound has been previously isolated from M. bontioides of Taiwan since 2017 and reported to exhibit MCF-7 cell proliferation. [11] Compound 3 was isolated as slightly yellow amorphous powder. It revealed the pseudomolecular ion peak at m/z 287 [M+H] + in the positive ESI-MS.…”