Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, Uttar Pradesh, India.
Jawaharlal Nehru University, New Delhi, India.
J Biochem Mol Toxicol. 2023 Nov;37(11):e23474. doi: 10.1002/jbt.23474. Epub 2023 Jul 21.
Flavonoids are among the largest groups of secondary metabolites. Studies suggest that dietary intake of flavonoids reduces the risk of cancer. 3,5,7-trihydroxyflavone (THF) belongs to the flavone class of flavonoids and potentially inhibits the growth of many cancers; however, it is unexplored in prostate cancer. This study reports the antiproliferative potential of THF in prostate cancer cell line via reactive oxygen species (ROS)-mediated cascades and examines the tumour reduction potential in swiss albino mice. The potency of THF was evaluated by employing cytotoxicity assays and wound healing assays. Cell cycle, ROS, mitochondrial membrane potential (MMP), and Annexin-V-FITC assay were performed using a flow cytometer. In vivo, anticancer potential was achieved using the mice Ehrlich Ascites Carcinoma (EAC) model. THF inhibits cell growth with IC of 64.30 µM (MTT), 81.22 µM (NRU) and 25.81 µM (SRB), substantiated by cell migration assay. Cell-cycle analysis revealed that THF increases the subdiploid population. Furthermore, the Annexin-V-FITC assay evoked a significant induction of late apoptosis at a higher concentration of THF. THF also disrupts MMP, caused by an increased generation of ROS. In the EAC model, THF significantly inhibits tumour growth and increases the percent survival of mice and ROS levels in EAC cells. Hence, it may be concluded that THF might execute its antiproliferative effect via inducing ROS generation and could be a promising lead for preclinical and clinical validations.
类黄酮是次生代谢产物中最大的一类。研究表明，饮食中类黄酮的摄入可以降低癌症的风险。3,5,7-三羟基黄酮（THF）属于黄酮类化合物，可能抑制多种癌症的生长；然而，它在前列腺癌中尚未得到探索。本研究通过活性氧（ROS）介导的级联反应报告了 THF 在前列腺癌细胞系中的抗增殖潜力，并在瑞士白化小鼠中检查了肿瘤减少的潜力。通过细胞毒性测定和划痕愈合测定来评估 THF 的效力。使用流式细胞仪进行细胞周期、ROS、线粒体膜电位（MMP）和 Annexin-V-FITC 测定。在体内，使用小鼠艾氏腹水癌（EAC）模型实现抗癌潜力。THF 通过 MTT（IC 为 64.30 µM）、NRU（IC 为 81.22 µM）和 SRB（IC 为 25.81 µM）抑制细胞生长，这一点得到细胞迁移测定的证实。细胞周期分析表明，THF 增加了亚二倍体群体。此外，在更高浓度的 THF 下，Annexin-V-FITC 测定引起晚期凋亡的显著诱导。THF 还破坏了 MMP，这是由于 ROS 的产生增加所致。在 EAC 模型中，THF 显著抑制肿瘤生长，提高了 EAC 细胞中小鼠的存活率和 ROS 水平。因此，可以得出结论，THF 可能通过诱导 ROS 产生来发挥其抗增殖作用，并且可能成为临床前和临床验证的有前途的先导物。
