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The genus Garcinia (family Cluseaceae) grows in tropical forests of Asia and Africa (Hemshekhar et al., 2011). Garcinia species have received some interest by industry due to producing potential medicinal and pharmacologically active chemical entities (Hemshekhar et al., 2011). Garcinia daedalanthera Pierre is a native Indonesian plant species that has not been studied for its chemical constituents or biological activities. Therefore, an opportunity was taken to explore the promising potential of this plant, as well as to conduct phytochemical studies, specifically in the area of cancer research.The aim of this study was to isolate active compounds from the leaves of G. daedalanthera. Structural analysis of the isolates was performed using 1D- and 2D-NMR, LC-MS and GC-MS, IR, polarimetry, and UV-visible physical and spectroscopic methods. Cytotoxicity-guided fractionation was carried out to prioritize fractions for isolating compounds of interest. The types of cell lines used in this cytotoxicity study were MDA-MB-231 and MCF-7 human breast, DU-145 and PC-3 prostate, HeLa cervical, and HT-29 colorectal cancer cell lines. ROS activity towards HT-29 cells was also observed to provide cell-based targeted biological activity data of the isolates. In this study, ten secondary metabolites were purified using combinations of column chromatography and HPLC. Eight known compounds, docosanedioic acid (150), 2,5-dimethylnonadecane (151), lupeol (152), stigmasterol (153), β-sitosterol (154), heptadecanoic acid (156), hexanedioic acid, 1,6-bis[(2R)-ethylhexyl] ester (158), and 1,3-di-O-[2’,2’-di-(p-phenylene)] (159) were identified. Also, two new compounds, (S)-2-hydroxy-3-(octanoyloxy)propyl pentacosanoate (155) and (S)-3-(((S)-11-acetoxyoctadecanoyl)oxy)propane-1,2-diyl diacetate (157) were structurally elucidated. Compound 152 showed weak cytotoxicity towards HT-29 cells with an IC50 value of 19.2 µM. The other isolated compounds did not exhibit any cytotoxicity towards the cancer cell lines at 20 µg/mL. In a ROS assay, compounds 153 showed ROS induction at 50 µM by ~1.24 fold in ROS-induced HT-29 cells. This result suggested that this compound potentially have a role as adjuvant therapy in cancer related to ROS activation. Compound 156 was found to possess a similar level of ROS induction activity (~1.48 fold induction at 0.5 µM) to daunomycin (positive control) (~1.25 fold induction at 0.4 µM) in HT-29 cells both pretreated or untreated by ROS inducers. This suggested that 156 may have beneficial chemotherapeutic activity using other types of cancer cell lines or in other diseases states related to ROS activation. Cell protective effects via ROS inhibition towards HT-29 cell lines pretreated by ROS inducers were observed for compounds 150, 151, 155, 157, and 158, in a dose-dependent manner. Compound 151 showed the highest ROS inhibition in HT-29 cells (36.12%) followed by compound 157 (10%), at 50 µM. These compounds potentially had a chemopreventive action in cancer management. This research represents the first findings of the investigation of potential cancer chemopreventive and chemotherapeutic properties of G. daedalanthera leaves via ROS activity. |
