Simanurak Orakot, Pekthong Dumrongsak, Somran Julintorn, Wangteeraprasert Apirath, Srikummool Metawee, Kaewpaeng Naphat, Parhira Supawadee, Srisawang Piyarat
Department of Physiology, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand.
Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok 65000, Thailand.
Heliyon. 2023 Jul 7;9(7):e18013. doi: 10.1016/j.heliyon.2023.e18013. eCollection 2023 Jul.
stem bark extract, particularly the dichloromethane fraction (CGDCM), demonstrated the most potent antiproliferative effects on hepatocellular carcinoma HepG2 and colorectal HCT116 cells. The current study focused on enhancing the effectiveness of cancer treatment with CGDCM at concentrations close to the IC50 in HCT116 cells by reducing their nutrient supply. CGDCM (2, 4, and 8 μg/mL) treatment for 24 h under glucose conditions of 4.5 g/L without fetal bovine serum (FBS) supplementation or serum starvation (G+/F-), glucose 0 g/L with 10% FBS or glucose starvation (G-/F+), and glucose 0 g/L with 0% FBS or complete starvation (G-/F-) induced a greater antiproliferative effect in HCT116 cells than therapy in complete medium with glucose 4.5 g/L and 10% FBS (G+/F+). Nonetheless, the anticancer effect of CGDCM at 4 μg/mL under (G-/F-) showed the highest activity compared to other starvation conditions. The three starvation conditions showed a significant reduction in cell viability compared to the control (G+/F+) medium group, while the inhibitory effect on cell viability did not differ significantly among the three starvation conditions. CGDCM at 4 μg/mL in (G-/F-) medium triggered apoptosis by dissipating the mitochondrial membrane potential and arresting cells in the G2/M phase. This investigation demonstrated that a decrease in intracellular ATP and fatty acid levels was associated with enhanced apoptosis by treatment with CGDCM at 4 μg/mL under (G-/F-) conditions. In addition, under (G-/F-), CGDCM at 4 μg/mL increased levels of reactive oxygen species (ROS) and was suggested to primarily trigger apoptosis in HCT116 cells. Thus, extracts may be useful for the future development of alternative, effective cancer treatment regimens.
茎皮提取物，特别是二氯甲烷部分（CGDCM），对肝癌HepG2细胞和结肠直肠癌HCT116细胞表现出最有效的抗增殖作用。当前的研究聚焦于通过减少HCT116细胞的营养供应来增强接近IC50浓度的CGDCM对癌症的治疗效果。在不添加胎牛血清（FBS）或血清饥饿（G+/F-）的4.5 g/L葡萄糖条件下、添加10% FBS的0 g/L葡萄糖或葡萄糖饥饿（G-/F+）条件下以及0% FBS的0 g/L葡萄糖或完全饥饿（G-/F-）条件下，用CGDCM（2、4和8 μg/mL）处理24小时，与在含有4.5 g/L葡萄糖和10% FBS的完全培养基（G+/F+）中进行的治疗相比，在HCT116细胞中诱导了更大的抗增殖作用。尽管如此，在（G-/F-）条件下4 μg/mL的CGDCM的抗癌效果与其他饥饿条件相比显示出最高的活性。与对照（G+/F+）培养基组相比，三种饥饿条件下细胞活力均显著降低，而三种饥饿条件对细胞活力的抑制作用无显著差异。在（G-/F-）培养基中4 μg/mL的CGDCM通过消散线粒体膜电位并使细胞停滞在G2/M期触发凋亡。该研究表明，在（G-/F-）条件下用4 μg/mL的CGDCM处理导致细胞内ATP和脂肪酸水平降低与凋亡增强相关。此外，在（G-/F-）条件下，4 μg/mL的CGDCM增加了活性氧（ROS）水平，并被认为主要在HCT116细胞中触发凋亡。因此，提取物可能对未来替代、有效的癌症治疗方案的开发有用。
