Kabir Syed Rashel, Islam Tofazzal, Mollah Md Nurul Haque
Department of Biochemistry and Molecular Biology, Faculty of Science, University of Rajshahi, Rajshahi, 6205, Bangladesh.
Institute of Biotechnology and Genetic Engineering (IBGE), Bangabandhu Sheikh Mujibur Rahman Agricultural University, Gazipur, 1706, Bangladesh.
Med Oncol. 2023 Mar 24;40(5):129. doi: 10.1007/s12032-023-01986-y.
Scientists are finding the most effective chemotherapeutic agents for the treatment of cancer. In the present study, we evaluated the anticancer mechanism of DPPG, a derivative of DAPG (2,4-diacetylphloroglucinol), for the first time. DPPG and DAPG inhibited 83 and 59% of human colorectal cancer HCT116 cell growth at 40.0 µg/ml, and 74 and 57% of human lung cancer A549 cell growth at 10.0 µg/ml concentrations respectively. Furthermore, DPPG and DAPG inhibited 97 and 73% colony formation of the HCT116 cells at 20.0 µg/ml concentration. DPPG and DAPG induced apoptosis in the HCT116 and A549 cells that was confirmed by Hoechst 33342 and FITC-annexin V staining. This result also revealed that ROS generated in both the HCT116 and A549 cells after treatment with DPPG. However, no ROS production was observed in HCT116 and A549 cells after treatment with DAPG. Both DAPG and DPPG significantly increased the CASP3 protein expression that was detected by staining the cells with the super-view 488-CASP3 substrate. Expression of WNT1 gene was eliminated in DPPG and DAPG treated HCT116. Expression of MAPK1 gene was entirely abolished in DPPG treated cells, whereas a significant decrease was observed for DAPG. An intense band of CASP8 gene product was observed agarose gel for DPPG treated HCT116 cells than DAPG. Molecular docking simulation showed the high binding affinities (≥ 6.5 kcal/mol) of DPPG and DAPG with target proteins WNT1, MAPK1, CASP8, and CASP3 in HCT116 cells. This manuscript demonstrated that DAPG and DPPG inhibited lung and colorectal cancer cells by inducing apoptosis. DAPG and DPPG inhibited A549 and HCT116 cells growth by inducing apoptosis.
科学家们正在寻找治疗癌症最有效的化疗药物。在本研究中，我们首次评估了DAPG（2,4 - 二乙酰基间苯三酚）的衍生物DPPG的抗癌机制。DPPG和DAPG在浓度为40.0μg/ml时分别抑制了83%和59%的人结肠直肠癌HCT116细胞生长，在浓度为10.0μg/ml时分别抑制了74%和57%的人肺癌A549细胞生长。此外，DPPG和DAPG在浓度为20.0μg/ml时分别抑制了HCT116细胞97%和73%的集落形成。DPPG和DAPG诱导HCT116和A549细胞凋亡，这通过Hoechst 33342和FITC - 膜联蛋白V染色得到证实。该结果还表明，用DPPG处理后，HCT116和A549细胞中均产生活性氧（ROS）。然而，用DAPG处理后，在HCT116和A549细胞中未观察到ROS产生。DAPG和DPPG均显著增加了通过用超视野488 - CASP3底物对细胞染色检测到的CASP3蛋白表达。在用DPPG和DAPG处理的HCT116中，WNT1基因的表达被消除。在用DPPG处理的细胞中，MAPK1基因的表达完全被消除，而在用DAPG处理的细胞中观察到显著下降。与DAPG相比，在用DPPG处理的HCT116细胞的琼脂糖凝胶上观察到CASP8基因产物的条带更强。分子对接模拟显示DPPG和DAPG与HCT116细胞中的靶蛋白WNT1、MAPK1、CASP8和CASP3具有高结合亲和力（≥6.5 kcal/mol）。本论文证明DAPG和DPPG通过诱导凋亡抑制肺癌和结肠直肠癌细胞。DAPG和DPPG通过诱导凋亡抑制A549和HCT116细胞生长。
