Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia.
Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia.
Asian Pac J Cancer Prev. 2023 May 1;24(5):1495-1505. doi: 10.31557/APJCP.2023.24.5.1495.
Triple negative breast cancer cells (TNBC) are a small part of cancer-inducing cells in breast cancer, which are characterized by high metastatic and self-renewal. Self-renewal has the ability to renew itself and loses control of proliferation. Curcuma longa extract (CL) and Phyllanthus niruri extract (PN) known to have anti-proliferative effects on cancer cells. However, the effects of combination CL and PN on TNBC proliferation still unclear.
This study aimed to evaluate the antiproliferative effects of the combination CL and PN on TNBC MDAMB-231 and attempted to elucidate the underlying molecular mechanisms.
The dried rhizomes of Curcuma longa and the herbs of Phyllanthus niruri were macerated with ethanol for 72 h.The antiproliferative and synergistic effects of combination CL and PN were investigated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Combination index values were calculated using CompuSyn (ComboSyn, Inc, Paramus, NJ). The cell cycle and apoptosis assay were determined by propidium iodide (PI) and PI-AnnexinV assay under flow cytometer, respectively. The intracellular ROS levels were evaluated using 2',7'-Dichlorodihydrofluorescein diacetate (DCFDA) assay. The mRNA expressions of proliferation-related genes in the cells were determined using bioinformatic assay.
The CL and PN single treatment caused a potent and dose-dependent decrease in the percentage of viable cells with IC50 value of 13 μg/mL and 45 μg/mL for 24 h, respectively. The combination index values of the different combinations ranged from 0.08 - 0.90, indicating slightly strong to very strong synergistic effects. The combination of CL and PN also remarkably induced the S- and G2/M-phases cell cycle arrest that leading to apoptosis induction. Furthermore, the combination of CL and PN treatment induced the intracellular reactive oxygen species (ROS) levels. Mechanistically, the AKT1, EP300, STAT3 and EGFR signaling as potential targets of combination CL and PN in antiproliferation and antimetastatic of TNBC.
The combination of CL and PN exerted promising antiproliferative effects in TNBC. Therefore, CL and PN may be considered a potential source for the development of potent anticancer drugs for breast cancer treatment.
三阴性乳腺癌细胞（TNBC）是乳腺癌中诱导癌细胞的一小部分，其特征是转移性和自我更新能力高。自我更新具有自我更新的能力并且失去了对增殖的控制。姜黄提取物（CL）和叶下珠提取物（PN）已被证明对癌细胞具有抗增殖作用。然而，CL 和 PN 联合对 TNBC 增殖的影响尚不清楚。
本研究旨在评估 CL 和 PN 联合对 TNBC MDAMB-231 的抗增殖作用，并试图阐明潜在的分子机制。
用乙醇浸泡姜黄的干根茎和叶下珠的草药 72 小时。使用 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四唑溴盐（MTT）测定 CL 和 PN 联合的抗增殖和协同作用。使用 CompuSyn（Combosyn，Inc，Paramus，NJ）计算组合指数值。通过碘化丙啶（PI）和 PI-AnnexinV 测定分别在流式细胞仪下测定细胞周期和凋亡。使用 2'，7'-二氯二氢荧光素二乙酸酯（DCFDA）测定细胞内 ROS 水平。使用生物信息学测定法测定细胞中与增殖相关的基因的 mRNA 表达。
CL 和 PN 单一处理导致细胞存活率百分比呈浓度依赖性下降，24 小时的 IC50 值分别为 13 μg/mL 和 45 μg/mL。不同组合的组合指数值范围为 0.08-0.90，表明存在轻微强到很强的协同作用。CL 和 PN 的组合还显著诱导了 S 和 G2/M 期细胞周期阻滞，导致凋亡诱导。此外，CL 和 PN 处理诱导了细胞内活性氧（ROS）水平。从机制上讲，AKT1、EP300、STAT3 和 EGFR 信号作为 CL 和 PN 在 TNBC 中的增殖和转移抑制中的潜在靶点。
CL 和 PN 的联合在 TNBC 中表现出有希望的抗增殖作用。因此，CL 和 PN 可能被认为是开发用于乳腺癌治疗的有效抗癌药物的潜在来源。
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