NADPH: Quinone oxidoreductase 1 (NQO1) mediated anti-cancer effects of plumbagin in endocrine resistant MCF7 breast cancer cells,Phytomedicine

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NADPH: Quinone oxidoreductase 1 (NQO1) mediated anti-cancer effects of plumbagin in endocrine resistant MCF7 breast cancer cells
Phytomedicine ( IF 6.7 ) Pub Date : 2019-11-11 , DOI: 10.1016/j.phymed.2019.153133
Nalinee Pradubyat ₁ , Nithidol Sakunrangsit ₁ , Apiwat Mutirangura ₂ , Wannarasmi Ketchart ₁

Affiliation

Background

PLB is a natural naphthoquinone compound isolated from the roots of Plumbago indica plant. Our previous study reported the inhibitory effect of Plumbagin (PLB) on human endocrine resistant breast cancer cell growth and cell invasion.

Hypothesis/Purpose

Since PLB is a naphthoquinone compound, it can be reduced by the cytosolic NADPH: quinone oxidoreductase 1 (NQO1) enzyme. NQO1 expression is upregulated in various types of aggressive cancer including breast cancer. This study investigated the impact of NQO1 on anti-cancer effects of PLB in endocrine-resistant breast cancer cells.

Study Design

This study was an in vitro study using ER-positive cell line (MCF7) and endocrine-resistant cell lines (MCF7/LCC2 and MCF7/LCC9 cells).

Methods

The roles of NQO1 in anti-cancer activity of PLB were investigated by using NQO1 knockdown cells, NQO1 inhibitor and NQO1 overexpressed cells. To study the impact of NQO1 on the effects of PLB on cell viability, apoptosis, invasion and generation of ROS, the following assays were used: MTT assays, annexin V-PE/7-ADD staining flow cytometry, matrigel invasion assays and DCFHDA assays. To study the mechanism of how NQO1 mediated PLB effects in tamoxifen response and apoptosis, we assessed the levels of mRNA expression by using qRT-PCR.

Results

1. In this study, NQO1 was upregulated in endocrine-resistant cells.

2. PLB did not change the expression of NQO1 but it was able to increase NQO1 activity.

3. The inhibitory effects of PLB on cell proliferation, cell invasion and expression of tamoxifen resistant gene were attenuated in NQO1 knockdown cells or in the presence of NQO1 inhibitor.

4. The effects of PLB to induce apoptosis and generate ROS were also decreased when NQO1 activity was inhibited or when the NQO1 expression was reduced.

5. The anti-cancer effects of PLB increased when NQO1 was upregulated.

Conclusion

The effects of PLB in endocrine-resistant breast cancer cells is dependent on NQO1’s activity.

中文翻译：

NADPH：醌氧化还原酶 1 (NQO1) 介导的白铅素对内分泌耐药 MCF7 乳腺癌细胞的抗癌作用

背景

PLB 是一种从 Plumbago indica 植物根中分离出来的天然萘醌化合物。我们之前的研究报道了红花素 (PLB) 对人内分泌抗性乳腺癌细胞生长和细胞侵袭的抑制作用。

假设/目的

由于 PLB 是一种萘醌化合物，它可以被细胞溶质 NADPH：醌氧化还原酶 1 (NQO1) 酶还原。NQO1 表达在包括乳腺癌在内的各种侵袭性癌症中上调。本研究调查了 NQO1 对 PLB 在内分泌耐药乳腺癌细胞中的抗癌作用的影响。

学习规划

本研究是使用 ER 阳性细胞系 (MCF7) 和内分泌抗性细胞系（MCF7/LCC2 和 MCF7/LCC9 细胞）进行的体外研究。

方法

通过使用 NQO1 敲低细胞、NQO1 抑制剂和 NQO1 过表达细胞研究 NQO1 在 PLB 抗癌活性中的作用。为了研究 NQO1 对 PLB 对细胞活力、凋亡、侵袭和 ROS 产生的影响的影响，使用了以下测定：MTT 测定、膜联蛋白 V-PE/7-ADD 染色流式细胞术、基质胶侵袭测定和 DCFHDA 测定. 为了研究 NQO1 如何在他莫昔芬反应和细胞凋亡中介导 PLB 作用的机制，我们使用 qRT-PCR 评估了 mRNA 表达水平。