Wikstromol from Wikstroemia indica induces apoptosis and suppresses migration of MDA-MB-231 cells via inhibiting PI3K/Ak
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Wikstromol from Wikstroemia indica induces apoptosis and suppresses migration of MDA‑MB‑231 cells via inhibiting PI3K/Akt pathway Huankai Yao1 · Xiuli Zhang2 · Nan Zhang1 · Jindong Li3 · Yan Li1 · Qunli Wei1 Received: 16 April 2020 / Accepted: 23 August 2020 © The Japanese Society of Pharmacognosy 2020
Abstract Triple negative breast cancer (TNBC) is the most severe type of breast cancer due to the lack of specific targets and rapid metastasis, which result in the poor prognosis. Recently, phosphatidylinositol 3-kinase (PI3K)/Akt pathway has emerged as a potential target for the treatment of TNBC. In our research interest to discover phytochemicals targeting TNBC, we have investigated wikstromol from Wikstroemia indica using the human TNBC MDA-MB-231 cells. The results showed wikstromol at 10 μM inhibited cell growth of MDA-MB-231 cells which was confirmed by MTT assay. Further DAPI staining has revealed wikstromol at 10 μM induced apoptosis of cancer cells, which was associated with the activation of caspase-3 following down-regulation of Bcl-2 as well as up-regulation of Bax, cleaved PARP and phosphorylated p53. Meanwhile, it was observed at 0.1 μM wikstromol suppressed the migration of the cancer cells via decreasing transcription of NF-κB and reducing activity and secretion of downstream MMP-9. In addition, p-PI3K and p-Akt were down-regulated in MDAMB-231 cells in the presence of wikstromol at 0.1 μM, which indicated inactivation of PI3K/Akt pathway was involved in these inhibitory effects. Keywords Wikstromol · MDA-MB-231 cells · Apoptosis · Migration · PI3K/Akt pathway
Introduction Breast cancer is the most common cancer and the major cause of cancer-related death in females worldwide [1]. Of all subtypes of breast cancer, triple negative breast cancer (TNBC) accounts for about 15–20% [2]. Due to the lack of expression of estrogen receptor (ER), progesterone receptor (PR) and HER2, patients with this disease do not benefit from endocrine therapy. Meanwhile, owning to an inherently aggressive clinical behavior of TNBC as well as despondent targeted therapies, chemotherapy remains the only therapeutic option for patients [3, 4]. However, deficiency
* Yan Li [email protected] 1
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, No. 209 Tongshan Road, Xuzhou 221004, Jiangsu, China
2
Shanxian Central Hospital, Heze 274300, Shandong, China
3
Department of Pharmacy, The Hospital Affiliated to Nanjing University of Traditional Chinese Medicine (Taizhou People’s Hospital), Taizhou 225300, Jiangsu, China
of specific molecular targets for therapy and the metastasis have resulted in the poor prognosis of TNBC [5]. Recently, phosphatidylinositol 3-kinase (PI3K)/Akt pathway has emerged as a potential target for the treatment of TNBC [6]. Under normal condition, PI3K affords the integration of extracellular growth signals into the intracellular actions to initiate cell cycle progression [7]. As a serine/threonine kinase, Akt is the m
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