flavokawain-C and Colonic-Neoplasms

flavokawain-C has been researched along with Colonic-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for flavokawain-C and Colonic-Neoplasms

ArticleYear
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 = Biomedecine & pharmacotherapie, 2021, Volume: 137

    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.

    Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Apoptosis Regulatory Proteins; Biomarkers; Body Weight; Caspase 3; Cell Proliferation; Chalcones; Cisplatin; Colonic Neoplasms; Endoplasmic Reticulum Chaperone BiP; Female; HCT116 Cells; Humans; Kava; Mice; Mice, Inbred BALB C; Mice, Nude; Proteomics; Xenograft Model Antitumor Assays

2021
Flavokawain C Inhibits Cell Cycle and Promotes Apoptosis, Associated with Endoplasmic Reticulum Stress and Regulation of MAPKs and Akt Signaling Pathways in HCT 116 Human Colon Carcinoma Cells.
    PloS one, 2016, Volume: 11, Issue:2

    Flavokawain C (FKC) is a naturally occurring chalcone which can be found in Kava (Piper methysticum Forst) root. The present study evaluated the effect of FKC on the growth of various human cancer cell lines and the underlying associated mechanisms. FKC showed higher cytotoxic activity against HCT 116 cells in a time- and dose-dependent manner in comparison to other cell lines (MCF-7, HT-29, A549 and CaSki), with minimal toxicity on normal human colon cells. The apoptosis-inducing capability of FKC on HCT 116 cells was evidenced by cell shrinkage, chromatin condensation, DNA fragmentation and increased phosphatidylserine externalization. FKC was found to disrupt mitochondrial membrane potential, resulting in the release of Smac/DIABLO, AIF and cytochrome c into the cytoplasm. Our results also revealed that FKC induced intrinsic and extrinsic apoptosis via upregulation of the levels of pro-apoptotic proteins (Bak) and death receptors (DR5), while downregulation of the levels of anti-apoptotic proteins (XIAP, cIAP-1, c-FlipL, Bcl-xL and survivin), resulting in the activation of caspase-3, -8 and -9 and cleavage of poly(ADP-ribose) polymerase (PARP). FKC was also found to cause endoplasmic reticulum (ER) stress, as suggested by the elevation of GADD153 protein after FKC treatment. After the cells were exposed to FKC (60μM) over 18hrs, there was a substantial increase in the phosphorylation of ERK 1/2. The expression of phosphorylated Akt was also reduced. FKC also caused cell cycle arrest in the S phase in HCT 116 cells in a time- and dose-dependent manner and with accumulation of cells in the sub-G1 phase. This was accompanied by the downregulation of cyclin-dependent kinases (CDK2 and CDK4), consistent with the upregulation of CDK inhibitors (p21Cip1 and p27Kip1), and hypophosphorylation of Rb.

    Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Caspases; Cell Cycle; Cell Line, Tumor; Cell Survival; Chalcones; Colonic Neoplasms; DNA Fragmentation; Endoplasmic Reticulum Stress; Enzyme Activation; HCT116 Cells; HT29 Cells; Humans; MAP Kinase Signaling System; MCF-7 Cells; Membrane Potential, Mitochondrial; Phosphatidylserines; Proto-Oncogene Proteins c-akt; Receptors, Death Domain; Signal Transduction

2016