Nagaraj Bharathkumar, Sivasubramanian Arvind, Musthafa Shazia Anjum, Muhammad Sadiq, Anilkumar Aswathy Karanath, Munuswamy-Ramanujam Ganesh, Kamaraj Chinnaperumal, Dhanasekaran Sivaraman, Subramaniyan Vetriselvan
Interdisciplinary Institute of Indian System of Medicine (IIISM), SRM Institute of Science and Technology (SRMIST), Kattankulathur, 603203, Tamil Nadu, India; Department of Biotechnology, Faculty of Science and Humanities, SRM-IST, Kattankulathur, Chennai 603203, India.
Natural Products and Organic Synthesis Laboratory, Department of Chemistry, School of Chemical and Biotechnology, SASTRA Deemed to Be University, Thanjavur, 613401, Tamil Nadu, India.
Free Radic Biol Med. 2024 Nov 20;225:925-932. doi: 10.1016/j.freeradbiomed.2024.10.275. Epub 2024 Oct 10.
3-deoxycaryoptinol (Clerodin) is a clerodane diterpene isolated from the leaves of Clerodendrum infortunatum. The present research investigates the anticancer therapeutic efficacy of clerodin in human monocytic leukemic (THP-1) cells for the first time. In vitro assay using THP-1 cells showed the cytotoxic ability of clerodin. Further, Annexin-V(FITC)/PI and intracellular ROS (DCFDA) assays carried out using flow cytometry, and confocal laser scanning microscopy confirmed the apoptotic potential of clerodin. Moreover, the Western blot was used to detect mitochondrial apoptosis of THP-1 cells. RT-PCR, ELISA, and Western blot analysis clearly indicated that clerodin significantly increased the expression of pro-apoptotic marker caspase-3 in THP-1 cells. clerodin also selectively targeted the G2/M phase of THP-1 cells, a key feature for anticancer molecules. Importantly, the clerodin did not exhibit cytotoxicity against human peripheral blood cells. These properties of clerodin make it a potential chemotherapeutic agent that can selectively induce apoptosis in leukemia-like cancer cells.
3-脱氧假荆芥内酯(克罗迪因)是从臭牡丹叶中分离出的一种克罗烷二萜。本研究首次调查了克罗迪因对人单核细胞白血病(THP-1)细胞的抗癌治疗效果。使用THP-1细胞进行的体外试验显示了克罗迪因的细胞毒性能力。此外,通过流式细胞术进行的膜联蛋白-V(FITC)/碘化丙啶和细胞内活性氧(二氯荧光素二乙酸酯)检测,以及共聚焦激光扫描显微镜证实了克罗迪因的凋亡潜力。此外,蛋白质免疫印迹法用于检测THP-1细胞的线粒体凋亡。逆转录聚合酶链反应、酶联免疫吸附测定和蛋白质免疫印迹分析清楚地表明,克罗迪因显著增加了THP-1细胞中促凋亡标志物半胱天冬酶-3的表达。克罗迪因还选择性地靶向THP-1细胞的G2/M期,这是抗癌分子的一个关键特征。重要的是,克罗迪因对人外周血细胞没有细胞毒性。克罗迪因的这些特性使其成为一种潜在的化疗药物,能够在白血病样癌细胞中选择性地诱导凋亡。