Rahma Diyan Martha, Fatimah, Syahputra Wibowo, Bantari Wisynu Kusuma Wardhani, Josephine Elizabeth Siregar, Elisabeth Farah Novita Coutrier, Alfia Fitrianita, Andri Pramesyanti Pramono, Ita Margaretha Nainggolan, Yudhi Nugraha, Danar Danar, Naufal Abiyyu, Hesty Parbuntari, Lalu Unsunnidhal, Aswin Rafif Khairullah, Arif Nur Muhammad Ansori, Wimbuh Tri Widodo
Majapahit plant (Crescentia cujete), commonly found in Indonesia, has not been extensively explored for its medicinal properties. Given that many cancer treatments are derived from plants, this study aimed to examine the effects of plants on cancer chemical composition of the C. cujete fruit pulp extract, identify its primary compounds, and assess its potential as an antioxidant, anticancer agent, particularly for breast cancer. An insilico approach was used to evaluate the toxicity and interactions, of the compounds with cancer biomarker proteins, in addition to an in vivo Brine Shrimp Lethality Test (BSLT) for BSLT, toxicity screening using six concentrations of the extract (100, 200, 300, 400, and 600 ppm). The extract was obtained by boiling the fruit pulp in distilled water. Compound analysis using liquid chromatography-mass spectrometry (LC-MS) identified approximately 110 compounds, with kaempferol-3-O-rhamnoside (3.29%) and hesperidin (3.19%) being the most abundant. Toxicity analysis using ProTox 3.0 revealed that kaempferol-3-O-rhamnoside exhibited toxicity to the kidney, heart, and lungs, with probabilities of 0.68, 0.82, and 0.51, respectively. Hesperidin was toxic to the kidney and lungs, with probabilities of 0.76 and 0.66. Molecular docking studies with the X-ray spectrometer BRCA1 (P38398-BRCA1_HUMAN) and BRCA2 (P51587–BRCA2_HUMAN) proteins showed that kaempferol-3-Orhamnoside formed stable interactions with both proteins, with binding affinities of −7.0 kcal/mol for BRCA1 and-8.1 kcal/mol for BRCA2. Similarly, hesperidin demonstrated stable binding interactions with BRCA1 (binding affinity) of −7.7 kcal/mol) and BRCA2 (binding affinity of −9.0 kcal/mol). The LC50 value for the C. cujete fruit pulp extract was calculated as follows: determined to be 546 ppm (95% CI: 498.3–592.1 ppm), indicating that the extract is toxic and holds potential as an anticancer agent. While individual compounds exhibited organ-specific toxicity, the overall extract was nontoxic, suggesting its potential for further anticancer research. Future studies should focus on additional toxicity testing using cell cultures and mammalian models. © 2026, Universitas Indonesia. All rights reserved.
Department of Pharmacy, STIKES Karya Putra Bangsa, Tulungagung, 66291, Indonesia; Biotechnology Study Program, Graduate School, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia; Department of Medical Laboratory Technology, STIKES Karya Putra Bangsa, Tulungagung, 66291, Indonesia; Eijkman Research Center for Molecular Biology, National Research and Innovation Agency, Cibinong, 16911, Indonesia; Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency, Cibinong, 16911, Indonesia; Biotechnology Study Program, Graduate School, Bogor Agricultural University, Bogor, 16680, Indonesia; Department of Chemistry, Faculty of Mathematics and Science, Universitas Negeri Malang, Malang, 65145, Indonesia; Department of Biochemistry, Faculty of Mathematics and Natural Sciences, Bogor Agricultural University, Bogor, 16680, Indonesia; Department of Chemistry, Universitas Negeri Padang, Padang, 25131, Indonesia; Institute of Organic Chemistry, Heidelberg University, Heidelberg, 69120, Germany; Molecular Bioengineering Laboratory, Bioagricultural Sciences Study Program, Graduate School, Department of Applied Life Sciences, Nagoya University, Nagoya, 464-8601, Japan; Research Center for Veterinary Science, National Research and Innovation Agency, Bogor, 16911, Indonesia; Master Program of Immunology, Postgraduate School, Universitas Airlangga, Surabaya, 60286, Indonesia; Master Program of Forensic Science, Postgraduate School, Universitas Airlangga, Surabaya, 60286, Indonesia; Human Genetic Laboratory, Institute of Tropical Desease, Universitas Airlangga, Surabaya, 60115, Indonesia
