Department of Laboratory Hematology and Blood Bank, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Traditional Medicine and Materia Medica Research Center, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Nutr Cancer. 2020;72(6):1043-1056. doi: 10.1080/01635581.2019.1665188. Epub 2019 Sep 23.
Gaillardin (GLN) is a sesquiterpene lactone isolated from the chloroform extract of L. This natural compound has shown cytotoxicity in various cancerous cell line. However, its effect on leukemic cells is ambiguous. Due to the neurotoxicity of vincristine (VCR) in acute lymphoblastic leukemia (ALL), we aimed to examine the cytotoxic effects of GLN alone and in combination with vincristine on induction of apoptosis, and cell cycle progression in ALL cell lines (NALM-6 and MOLT-4). Our results displayed that GLN could induce cytotoxic effects in MOLT-4 and NALM-6 with IC values of 7.3 and 6.1 μM, respectively. In this study, we demonstrated that GLN induces cytotoxicity through G0/G1 phase arrest followed by apoptosis in a dose-dependent manner. Fortunately, this natural compound did not show significant cytotoxic effects on normal cells. This study demonstrated that GLN was capable to extend chemotherapeutic sensitivity in ALL cells by reducing VCR concentration without constraining its effectiveness. Therefore, it might act as a promising anticancer agent for the treatment of leukemia.
加兰他敏（GLN）是从 中氯仿提取物中分离得到的一种倍半萜内酯。这种天然化合物已显示出对各种癌细胞系的细胞毒性。然而，其对白血病细胞的影响尚不清楚。由于长春新碱（VCR）在急性淋巴细胞白血病（ALL）中的神经毒性，我们旨在研究 GLN 单独和与长春新碱联合应用对诱导 ALL 细胞系（NALM-6 和 MOLT-4）凋亡和细胞周期进展的细胞毒性作用。我们的结果显示，GLN 可以分别以 7.3 和 6.1 μM 的 IC 值诱导 MOLT-4 和 NALM-6 的细胞毒性作用。在这项研究中，我们证明 GLN 通过 G0/G1 期阻滞，随后以剂量依赖性方式诱导细胞凋亡，从而诱导细胞毒性。幸运的是，这种天然化合物对正常细胞没有明显的细胞毒性作用。这项研究表明，GLN 通过降低 VCR 浓度而不影响其疗效，从而提高 ALL 细胞的化疗敏感性。因此，它可能是治疗白血病的一种有前途的抗癌药物。
