Anti-cancer effects of methanol-ethyl acetate partitioned fraction from Magnolia grandiflora in human non-small cell lun

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Anti-cancer effects of methanol-ethyl acetate partitioned fraction from Magnolia grandiflora in human non-small cell lung cancer H1975 cells Hui Ma 1 & Xiangjian Bai 1 & Xiaolong Sun 1 & Bohan Li 1 & Meilin Zhu 1 & Yiqun Dai 1 & Qiang Huo 1 & Hong-Mei Li 1 & Cheng-Zhu Wu 1 Received: 31 October 2019 / Accepted: 2 March 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Non-small cell lung cancer (NSCLC) constitutes nearly 85% of all cases of lung cancer. Drug resistance, dose-limiting toxicity, and metastasis in NSCLC eventually reduce the efficacy of chemotherapeutics. In this study, we have shown that the methanolethyl acetate partitioned fraction from Magnolia grandiflora L. seeds (MEM) exhibit potential anti-cancer activities against NSCLC H1975 cells in vivo and in vitro. MEM significantly inhibited the proliferation of H1975 cells in a concentration- and time-dependent manner. Further, MEM exhibited potent anti-tumor efficacy and low toxicity in nude mice bearing H1975 tumors. Our study also showed that MEM could induce cellular apoptosis in H1975 cells by down-regulating the protein expression levels of Akt and p-Akt-473, and by increasing the ratio of Bax/Bcl-2. Also, MEM significantly inhibited metastasis-related cell invasion and migration of H1975 cells, which associated with the down-regulation of HIF-1α, MMP-2, and MMP-9 protein expression levels. Thus, our data shows that MEM may be an effective fraction of M. grandiflora in NSCLC treatment. Keywords Magnolia grandiflora . Non-small cell lung cancer . Apoptosis . Invasion . Migration

Introduction Lung cancer is one of the most common causes of cancer and life ends in death (Bray et al. 2012). Non-small cell lung cancer (NSCLC) accounts for 85% cases of lung cancer cases and has been treated by drugs targeting receptor tyrosine kinases, mainly the epidermal growth factor receptor (EGFR) family (Jemal et al. 2011; Lynch et al. 2006). In the past several years, EGFR-tyrosine kinase inhibitor (TKI), gefitinib (Iressa), and erlotinib (Tarceva), have been the eutherapeutics for patients with NSCLC (Mitsudomi et al. 2010). However,

Hui Ma and Xiangjian Bai contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10863-020-09828-6) contains supplementary material, which is available to authorized users. * Cheng-Zhu Wu [email protected] 1

School of Pharmacy, Bengbu Medical College, 233030 Bengbu, Anhui, China

acquired drug-resistance and side effects universally developed in many patients that responded to EGFR-TKIs (Jackman et al. 2010; Lu et al. 2018). Therefore, research and development efforts for discovering highly effective and low toxicity anti-NSCLC drugs have become indispensable for the treatment of NSCLC. Traditional Chinese medicine (TCM) and natural medicine can serve as one of the most important sources for discovering new drugs with several advantages, such as unique biological activities, multiple targets, low toxicity, and the a