苦杏仁苷在体外阻断乳腺癌 DNA 复制中的作用。

Role of Amygdalin in Blocking DNA Replication in Breast Cancer In Vitro.

机构信息

Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.

出版信息

Curr Pharm Biotechnol. 2021;22(12):1612-1627. doi: 10.2174/1389201022666210203123803.

DOI:10.2174/1389201022666210203123803

PMID:33535947

Abstract

BACKGROUND

Amygdalin has anticancer benefits because of its active component, hydrocyanic acid. However, the underlying molecular mechanism is unclear.

OBJECTIVE

This study aimed to investigate the molecular mechanism by which amygdalin exerts antiproliferative effects in the human Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line.

METHODS

MCF-7 cells were exposed to amygdalin at a particular IC value for 24 and 48 hours and compared to non-treated cells. An Affymetrix whole-transcript expression array was used to analyze the expression of 32 genes related to DNA replication.

RESULTS

Among the 32 genes, amygdalin downregulated the expression of 16 genes and 19 genes by >1.5-fold at 24 and 48 hours, respectively. At 24 hours, the downregulated genes from the DNA polymerase α-primase complex were POLA1, POLA2, PRIM1, and PRIM2; DNA polymerase δ complex: POLD3; DNA polymerase ε complex: POLE4, Minichromosome Maintenance protein (MCM) complex (helicase): MCM2, MCM3, MCM4, MCM6, and MCM7; clamp and clamp loader: PCNA; nuclease: FEN1; and DNA ligase: LIG1. At 48 hours, the downregulated genes from the DNA polymerase α-primase complex were POLA1, POLA2, and PRIM1; DNA polymerase δ complex: POLD3; DNA polymerase ε complex: POLE and POLE2; MCM complex (helicase): MCM2, MCM3, MCM4, MCM5, MCM6, and MCM7; clamp and clamp loader: PCNA, RFC2, and RFC3; RNase H: RNASEH2A; nucleases: DNA2 and FEN1; and DNA ligase: LIG1.

CONCLUSION

Amygdalin treatment caused downregulation of several genes that play critical roles in DNA replication in the MCF-7 cell line. Thus, it might be useful as an anticancer agent.

摘要

背景

苦杏仁苷因其活性成分氰酸而具有抗癌益处。然而，其潜在的分子机制尚不清楚。

目的

本研究旨在探讨苦杏仁苷在人密歇根癌症基金会-7（MCF-7）乳腺癌细胞系中发挥抗增殖作用的分子机制。

方法

将 MCF-7 细胞暴露于特定 IC 值的苦杏仁苷中 24 和 48 小时，并与未经处理的细胞进行比较。使用 Affymetrix 全转录表达谱芯片分析与 DNA 复制相关的 32 个基因的表达。

结果

在 32 个基因中，苦杏仁苷分别在 24 小时和 48 小时下调了 16 个和 19 个基因的表达，倍数大于 1.5。在 24 小时时，DNA 聚合酶α-引发酶复合物中的下调基因有 POLA1、POLA2、PRIM1 和 PRIM2；DNA 聚合酶δ复合物：POLD3；DNA 聚合酶ε复合物：POLE4、微染色体维持蛋白（MCM）复合物（解旋酶）：MCM2、MCM3、MCM4、MCM6 和 MCM7；夹和夹加载器：PCNA；核酸内切酶：FEN1；和 DNA 连接酶：LIG1。在 48 小时时，DNA 聚合酶α-引发酶复合物中的下调基因有 POLA1、POLA2 和 PRIM1；DNA 聚合酶δ复合物：POLD3；DNA 聚合酶ε复合物：POLE 和 POLE2；MCM 复合物（解旋酶）：MCM2、MCM3、MCM4、MCM5、MCM6 和 MCM7；夹和夹加载器：PCNA、RFC2 和 RFC3；RNase H：RNASEH2A；核酸内切酶：DNA2 和 FEN1；和 DNA 连接酶：LIG1。