Department of Biochemistry, University of Dschang, P.O. Box 67, Dschang, Cameroon.
Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial- (CSIR-) Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, 700032, Kolkata, India.
Biomed Res Int. 2023 Feb 21;2023:8981430. doi: 10.1155/2023/8981430. eCollection 2023.
Despite the recent advancement of treatment strategies, cancer ranks 2 among the causes of death globally. Phytochemicals have gained popularity as an alternate therapeutic strategy due to their nontoxic nature. Here, we have investigated the anticancer properties of guttiferone BL (GBL) along with four known compounds previously isolated from . The cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The study was extended for the assessment of the effect of GBL in PA-1 cells apoptosis induction, cell cycle distribution, and change in mitochondrial membrane potential using flow cytometry, Western blot analysis, and real-time PCR. Among the five tested compounds, GBL displayed significant antiproliferative effects against all tested human cancer cells (IC < 10M). Moreover, GBL exhibited no significant cytotoxicity towards normal ovarian epithelial cell line (IOSE 364) up to 50 M. GBL induced sub-G cell cycle arrest and significant upregulation of cell cycle regulatory proteins of ovarian cancer cell PA-1. Furthermore, GBL induced its apoptosis as depicted by the accumulation of cells both at the early and late apoptotic phase in Annexin V/PI assay. In addition, it decreased the PA-1 mitochondrial membrane potential and promoted upregulation of caspase-3, caspase-9, and Bax and downregulation of Bcl-2. GBL also showed a dose-dependent inhibition of PA-1 migration. Altogether, this study reveals that guttiferone BL, studied herein for the first time, exhibits efficient antiproliferative activity by the induction of apoptosis through the mitochondrial-dependent pathway. Its investigation as a therapeutic agent against human cancers especially ovarian cancer should be envisaged.
尽管最近治疗策略有所进步，但癌症仍是全球死亡原因中的第 2 位。由于其无毒特性，植物化学物质作为一种替代治疗策略受到了广泛关注。在这里，我们研究了 guttiferone BL（GBL）以及先前从. 中分离出的四种已知化合物的抗癌特性。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）测定评估细胞毒性。该研究扩展到评估 GBL 在诱导 PA-1 细胞凋亡、细胞周期分布和线粒体膜电位变化中的作用，方法是使用流式细胞术、Western blot 分析和实时 PCR。在测试的五种化合物中，GBL 对所有测试的人类癌细胞均表现出显著的抗增殖作用（IC < 10M）。此外，GBL 对正常卵巢上皮细胞系（IOSE 364）的细胞毒性在 50μM 时不明显。GBL 诱导细胞周期停滞于亚 G1 期，并显著上调卵巢癌细胞 PA-1 的细胞周期调节蛋白。此外，GBL 通过在 Annexin V/PI 测定中积累处于早期和晚期凋亡阶段的细胞诱导其凋亡。此外，它降低了 PA-1 的线粒体膜电位并促进了 caspase-3、caspase-9 和 Bax 的上调以及 Bcl-2 的下调。GBL 还表现出剂量依赖性抑制 PA-1 迁移。总之，这项研究表明，guttiferone BL，在此首次研究，通过诱导线粒体依赖性途径的细胞凋亡来表现出有效的抗增殖活性。应考虑将其作为治疗人类癌症，特别是卵巢癌的药物进行研究。
