Chittasupho Chuda, Samee Weerasak, Mangmool Supachoke, Karuna Narainrit, Anuchapreeda Songyot, Okonogi Siriporn, Athikomkulchai Sirivan
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.
Center of Excellence in Pharmaceutical Nanotechnology, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand.
Int J Mol Sci. 2025 Mar 18;26(6):2729. doi: 10.3390/ijms26062729.
Cancer remains a significant global health challenge, necessitating novel therapeutic interventions. leaf extract (CCL) has gained interest for its potential anticancer properties due to its bioactive composition. This study aims to evaluate the cytotoxic effects of CCL against MCF-7 breast cancer and HeLa cervical cancer cells and elucidate its mechanisms of action. High-performance liquid chromatography identified verbascoside, isoverbascoside, and hispidulin as the major bioactive compounds. CCL exhibited time- and dose-dependent cytotoxicity, with MCF-7 cells showing greater sensitivity (IC = 126.8 µg/mL, 72 h) than HeLa cells (216.1 µg/mL, 72 h). Flow cytometry confirmed apoptotic induction, with late apoptosis increasing at moderate concentrations (16.03-23.55%) and necrosis prevailing at higher doses (50.80-63.68%). Reactive oxygen species generation was significantly elevated in MCF-7 (70.2%) and HeLa (60.4%) cells at 250 µg/mL. CCL effectively suppressed colony formation and cell migration in a dose-dependent manner. Molecular docking studies demonstrated that apoptosis induction of CCL bioactive compounds may mediate through the pro-apoptotic BCL2 associated X, apoptosis regulator (BAX) regulator. These findings highlight the potential of CCL as a natural anticancer agent with multiple mechanisms, including reactive oxygen species (ROS)-induced apoptosis, BAX activation, and inhibition of proliferation and metastasis.
癌症仍然是一项重大的全球健康挑战，需要新的治疗干预措施。叶提取物（CCL）因其生物活性成分具有潜在的抗癌特性而受到关注。本研究旨在评估CCL对MCF-7乳腺癌细胞和HeLa宫颈癌细胞的细胞毒性作用，并阐明其作用机制。高效液相色谱法鉴定出毛蕊花糖苷、异毛蕊花糖苷和海胆苷为主要生物活性化合物。CCL表现出时间和剂量依赖性细胞毒性，MCF-7细胞比HeLa细胞更敏感（72小时时IC = 126.8 µg/mL）（72小时时为216.1 µg/mL）。流式细胞术证实了凋亡诱导，中等浓度时晚期凋亡增加（16.03 - 23.55%），高剂量时坏死占主导（50.80 - 63.68%）。在250 µg/mL时，MCF-7细胞（70.2%）和HeLa细胞（60.4%）中的活性氧生成显著升高。CCL以剂量依赖性方式有效抑制集落形成和细胞迁移。分子对接研究表明，CCL生物活性化合物的凋亡诱导可能通过促凋亡的BCL2相关X凋亡调节因子（BAX）介导。这些发现突出了CCL作为一种具有多种机制的天然抗癌剂的潜力，这些机制包括活性氧（ROS）诱导的凋亡、BAX激活以及对增殖和转移的抑制。
