Phyllanthus emblica Fruit Extract Activates Spindle Assembly Checkpoint, Prevents Mitotic Aberrations and Genomic Instability in Human Colon Epithelial NCM460 Cells.

Xihan Guo,Xu Wang

doi:10.3390/ijms17091437

Abstract

The fruit of Phyllanthus emblica Linn. (PE) has been widely consumed as a functional food and folk medicine in Southeast Asia due to its remarkable nutritional and pharmacological effects. Previous research showed PE delays mitotic progress and increases genomic instability (GIN) in human colorectal cancer cells. This study aimed to investigate the similar effects of PE by the biomarkers related to spindle assembly checkpoint (SAC), mitotic aberrations and GIN in human NCM460 normal colon epithelial cells. Cells were treated with PE and harvested differently according to the biomarkers observed. Frequencies of micronuclei (MN), nucleoplasmic bridge (NPB) and nuclear bud (NB) in cytokinesis-block micronucleus assay were used as indicators of GIN. Mitotic aberrations were assessed by the biomarkers of chromosome misalignment, multipolar division, chromosome lagging and chromatin bridge. SAC activity was determined by anaphase-to- metaphase ratio (AMR) and the expression of core SAC gene budding uninhibited by benzimidazoles related 1 (BubR1). Compared with the control, PE-treated cells showed (1) decreased incidences of MN, NPB and NB (p < 0.01); (2) decreased frequencies of all mitotic aberration biomarkers (p < 0.01); and (3) decreased AMR (p < 0.01) and increased BubR1 expression (p < 0.001). The results revealed PE has the potential to protect human normal colon epithelial cells from mitotic and genomic damages partially by enhancing the function of SAC.

Highlights

Medicinal plants have been used as a resource of remedies for the treatment of various diseases since ancient times [1]
Frequencies of micronuclei (MN), nucleoplasmic bridge (NPB) and nuclear bud (NB) in cytokinesis-block micronucleus assay were used as indicators of Genomic Instability (GIN)
The data showed that, when compared to control, a steady increase in cell number was observed in 20–40 μg/mL Phyllanthus emblica Linn. (PE) cultures and the statistical significance was achieved at 40 μg/mL PE (p = 0.004)

Summary

Introduction

Medicinal plants have been used as a resource of remedies for the treatment of various diseases since ancient times [1]. Various studies showed that extracts from medicinal plants possess pharmacological activities including antioxidative, antigenotoxic and anticancer effects [3,4], as well as possess sub-acute and chronic toxicity including carcinogenic, genotoxic, and teratogenic effects [5]. These studies demonstrate that both the scientific validation of the ethno-medicinal claims and the safety evaluation are important for the expanding use of herbal plants in modern medicines. PE has been considered as a functional food due to the predominant medicinal functions beyond its adequate nutritional effects [10]

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