Effects of Cedrus atlantica extract on acute myeloid leukemia cell cycle distribution and apoptosis
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ORIGINAL ARTICLE
Effects of Cedrus atlantica extract on acute myeloid leukemia cell cycle distribution and apoptosis Pei‑Hsiu Hung1,2 · Ming‑Chang Hsieh3,4 · Shan‑Chih Lee5,6 · Xiao‑Fan Huang3,7 · Kai‑Fu Chang3,7 · Szu‑Yin Chen3 · Ming‑Shih Lee3,4 · Nu‑Man Tsai3,4 Received: 16 June 2020 / Accepted: 23 October 2020 © Springer Nature B.V. 2020
Abstract This study investigated the anti-leukemic effects of Cedrus atlantica extract (CAt extract) on cell cycle distribution and apoptosis in human acute myeloid leukemia (AML) cells. AML often occurs in older adults, accounting for 60% of the cases, and is likely to be resistant to chemotherapy due to multidrug resistance, resulting in early death during cancer treatment. With the increasing focus on prevention medicine, natural plant components are being used as a major source for the development of therapeutic drugs or functional foods to cure or alleviate the disease. Cedrus species are known to have anti-inflammatory, antimicrobial, antiviral, and anticancer effects; however, the anticancer effects of CAt extract have not been elucidated. In this study, CAt extract demonstrated an inhibitory effect on human leukemia cells in a concentration-dependent manner; CAt extract induced G 0/G1 phase arrest via restrained protein levels of p-Rb and cell cycle-related proteins. After CAt extract exposure, the extrinsic and intrinsic apoptotic pathways were activated through caspase-8, -9, and -3 cleavage. Additionally, CAt extract suppressed VEGF, MMP-2, and MMP-9 expression. This study demonstrated that CAt extract treatment significantly reduced cell growth, cell cycle arrest in the G0/G1 phase, and induction of apoptosis, leading to leukemia cell death. Keywords Cedrus atlantica · Apoptosis · Cell cycle · Acute myeloid leukemia (AML) Ming-Shih Lee and Nu-Man Tsai are corresponding authors contributed equally to this work.
Introduction
* Ming‑Shih Lee [email protected]
Acute myeloid leukemia (AML) is multidisciplinary disease characterized by various gene mutation which mediate proliferation and differentiation of cancer cells [1, 2]. Therapeutic options for leukemia are including chemotherapy, target therapy, radiation therapy, and hematopoietic stem cell transplantation. Overall 5-year survival which is less than 8% remains poor in older AML patients who are over 65 years due to comorbid disease and impaired bone marrow stem cell reserve [3–6]. Additionally, older patients are likely to have multidrug-resistant protein expression that affects the dosage of the chemo-drugs and the performance status of older patients is vulnerable to excess toxicity in chemotherapy, resulting in early mortality [7–9]. Despite the advances in understanding the molecular heterogeneity and pathogenesis of AML, there has been little progress in the standard therapy for AML. Hence, there is an urgent need for novel therapeutic agents with less toxicity for the treatment of AML. Previous studies have revealed several mechanisms involved in the chemopreventive effects of natural plant
* Nu‑
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