Urokinase plasminogen activator inhibitory and anti-breast cancer activity of Cananga odorata and Lantana camara leaf extracts from optimization of ultrasound-assisted extraction

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Bina Lohita Sari, Dien Puji Rahayu, Euis Julaeha, Syaikhul Aziz, Aulia Ilmiawati, Eli Yulia Sukmawati, Laili Salsabila Suddin Putri

2026 Pakistan Journal of Pharmaceutical Sciences Vol. 39 Issue 2 Article Cited by 1 Quartile

Abstract

Background: Cancer invasion and metastasis are complex processes that depend on the degradation of the extracellular matrix, largely facilitated by proteolytic enzymes such as urokinase-type plasminogen activator (uPA). Elevated levels of uPA have been consistently correlated with increased tumor aggressiveness and poorer clinical outcomes in breast cancer patients, making this enzyme a key therapeutic target. Flavonoids found in the hydroalcoholic leaf extracts of Cananga odorata (CO) and Lantana camara (LC) have previously been associated with inhibitory effects on cancer invasion and metastasis. Objectives: This study aimed to investigate the influence of different Ultrasound Assisted Extraction (UAE) method parameters, including ethanol concentration (50–90%), extraction time (10–50 minute), and temperature extraction (30–60 0C). The optimal UAE condition from CO and LC on total flavonoid content (TFC) and antioxidant activity (AA) were determined using Response Surface Methodology (RSM). The biological activities of the optimized extracts were further evaluated as uPA inhibition and cytotoxicity test. Methods: The TFC and AA were quantified using AlCl3 and DPPH assays, respectively. Additionally, the Urokinase Inhibitor Screening Kit was utilized to assess uPA inhibition, while the PrestoBlue assay was employed to measure cytotoxicity test against MCF-7 human breast cancer cells. Results: The optimal UAE conditions were 74% ethanol concentration, 31 minutes of extraction time, and an extraction temperature of 41°C resulted in extracts with high bioactive content, while LC showing superior TFC and stronger AA compared to CO. The results demonstrated that LC exhibited more potent bioactivities than CO leaf extract, with significantly lower IC50 values for uPA inhibition and cytotoxicity test were 24.13 ± 2.68 μg/mL and 42.87 ± 2.24 μg/mL). Conclusion: These findings suggest that LC extract effectively suppresses uPA activity while exerting cytotoxic effects on breast cancer cells, indicating its potential as a anticancer and chemoprevention agent. © 2026, Pakistan Journal of Pharmaceutical Sciences. All rights reserved.

Affiliations

Pharmacy Study Program, Faculty of Mathematics and Natural Sciences, Universitas Pakuan, West Java, Bogor, Indonesia; Research Center for Radiation Process Technology, Research Organization for Nuclear Energy-National Research and Innovation Agency (ORTN-BRIN), Jakarta, Indonesia; Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor, West Java, Indonesia; Department of Pharmacy, Faculty of Science, Institut Teknologi Sumatera, South Lampung, Indonesia; Departement of Chemistry, Faculty of Mathematics and Natural Sciences, IPB University, West Java, Bogor, Indonesia