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α-Mangostin reduced the viability of A594 cells in vitro by provoking ROS production through downregulation of NAMPT/NAD

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Cell Stress and Chaperones Aims and scope

Abstract

α-Mangostin (MAN) is a bioactive compound isolated from the inedible pericarp of a tropical fruit mangosteen (Garcinia mangostana Linn). It exhibits notable therapeutic potentials on lung cancers, but the underlying mechanisms are still largely unknown. This study was designed to further explore the mechanisms involved in cytotoxicity of MAN on A549 cells. Apoptosis and cell cycle distribution were analyzed by flow cytometry methods. The fluorescent probes DCFH-DA and JC-1 were used to assess the intracellular reactive oxidative species (ROS) and mitochondrial membrane potential statuses, respectively. The regulation of MAN on relevant pathways was investigated by immunoblotting assays. The results obtained indicated that MAN caused significant apoptosis and cell cycle arrest in A549 cells, which eventually resulted in inhibition on cell proliferation in vitro. All these phenomena were synchronized with escalated oxidative stress and downregulation of nicotinamide phosphoribosyltransferase/nicotinamide adenine dinucleotide (NAMPT/NAD). Supplementation with nicotinamide mononucleotide (NMN) and N-acetylcysteine (NAC) efficiently eased MAN-induced ROS accumulation, and potently antagonized MAN-elicited apoptosis and cell cycle arrest. The pro-apoptotic effect of MAN was further confirmed by increased expressions of cleaved caspase 3, 6, 7, and 9, and its effect on cell cycle progression was validated by the altered expressions of p-p38, p-p53, CDK4, and cyclin D1. The immunoblotting assays also demonstrated that NAC/NMN effectively restored these molecular changes elicited by MAN treatment. Collectively, this study revealed a unique anti-tumor mechanism of MAN by provoking ROS production through downregulation of NAMPT/NAD signaling and further validated MAN as a potential therapeutic reagent for lung cancer treatment.

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Funding

This work was supported by the National Natural Science Foundation of China (81603388), Talent Cultivation and International Academic Visiting Project for College Scholar of Anhui Province (gxfxZD2016163), Funding of “Peak” Training Program for Scientific Research of Yijishan Hospital, Wannan Medical College (GF2019J01), and Research Project on Traditional Chinese medicine of Anhui province (2016zy37).

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Author notes

  1. Yan-Yun Ding and Jia-Jie Luan contributed equally to this work.

Authors and Affiliations

  1. Yijishan Hospital, Wannan Medical College, Wuhu, 241000, China

    Yan-Yun Ding, Jia-Jie Luan, Yan Fan, Jing Song & Jian Zuo

  2. Faculty of Traditional Thai Medicine, Prince of Songkla University, Hat Yai, 90112, Thailand

    Opeyemi Joshua Olatunji

  3. Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu, 241000, China

    Jian Zuo

  4. Department of Pharmacy, Wannan Medical College, No 2nd West Zheshan Road, Wuhu, 241000, China

    Jian Zuo

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  1. Yan-Yun Ding
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Ding, YY., Luan, JJ., Fan, Y. et al. α-Mangostin reduced the viability of A594 cells in vitro by provoking ROS production through downregulation of NAMPT/NAD. Cell Stress and Chaperones 25, 163–172 (2020). https://doi.org/10.1007/s12192-019-01063-2

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