Phang, Chung-Weng and Abd Malek, Sri Nurestri and Karsani, Saiful Anuar (2021) Flavokawain C exhibits anti-tumor effects on in vivo HCT 116 xenograft and identification of its apoptosis-linked serum biomarkers via proteomic analysis. Biomedicine & Pharmacotherapy, 137. ISSN 0753-3322, DOI https://doi.org/10.1016/j.biopha.2020.110846.
Full text not available from this repository.Abstract
Chalcones and their derivatives belong to the flavonoid family. They have been extensively studied for their anticancer properties and some have been approved for clinical use. In this study, the in vivo anti-tumor activity of flavokawain C (FKC), a naturally occurring chalcone found in Kava (Piper methysticum Forst) was evaluated in HCT 116 cells (colon carcinoma). We also attempted to identify potential biomarkers and/or molecular targets in serum with applicability in predicting treatment outcome. The anti-tumor effects and toxicity of FKC were assessed using the xenograft nude mice model. Cisplatin was used as positive control. The anti-proliferative and apoptotic activities were then evaluated in tumor tissues treated with FKC. Furthermore, two-dimensional electrophoresis (2-DE) followed by protein identification using MALDI-TOF/TOF-MS/MS was performed to compare the serum proteome profiles between healthy nude mice and nude mice bearing HCT 116 tumor treated with vehicle solution and FKC, respectively. Our results showed that FKC treatment significantly inhibited HCT 116 tumor growth. In vivo toxicity studies showed that administration of FKC did not cause damage to major organs and had no significant effect on body weight. FKC was found to induce apoptosis in tumor, and this was associated with increased expression of cleaved caspase-3 and decreased expression of Ki67 in tumor tissues. Our proteomic analysis identified five proteins that changed in abundance Ig mu chain C region (secreted form), GRP78, hemopexin, kininogen-1 and apolipoprotein E. Overall, our findings demonstrated the potential of FKC as an anti-cancer agent for the treatment of colon carcinoma.
| Item Type: | Article |
|---|---|
| Funders: | Long Term Research Grant Scheme (LRGS) from the Ministry of Education Malaysia [LR003-2015] [LRGS/2014/UKM-UM/K/02], High Impact Research MoE from the Ministry of Education Malaysia [UM.C/625/1/HIR/MoE/SC/02] |
| Uncontrolled Keywords: | Flavokawain C; Anti-tumor; Colon cancer; Apoptosis; Serum biomarkers; Proteomics |
| Subjects: | R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica |
| Divisions: | Faculty of Science > Institute of Biological Sciences |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 13 Apr 2022 07:43 |
| Last Modified: | 13 Apr 2022 07:43 |
| URI: | http://eprints.um.edu.my/id/eprint/27038 |
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