Background
Methods
Animals/declarations for the animal research
Cell culture
Samples
Tumorigenesis assays
Western blotting
Cell proliferation assay
Viable cell count
Wound healing assay
Cell adhesion assay
Invasion assay
DNA microarray analysis
Quantitative real-time PCR
Statistical analysis
Results
Daphnane diterpenes suppressed B16F10 cells lung colonization
Daphnane diterpenes decreased the metastasis-associated proteins expression in mice lungs
Daphnane diterpenes have no effect on the proliferation and viability of B16F10 cells
Daphnane diterpenes inhibited cell migration, invasion, and cell adhesion
Effect of daphnane diterpenoid gnidilatidin on global gene expression in B16F10 cells
Gene | Function | Gnidilatidin (vs Control) |
---|---|---|
Egr1, early growth response 1 | Required for differentiation and mitogenesis; a cancer suppressor gene; activates expression of p53/TP53 and TGFB1, and thereby helps prevent tumor formation. | 113.24 |
Zfp36, zinc finger protein 36 | Plays a role in the regulation of keratinocyte proliferation, differentiation and apoptosis; Plays a role as a tumor suppressor by inhibiting cell proliferation in breast cancer cells. | 30.69 |
Fos, FBJ osteosarcoma oncogene Junb, Jun-B oncogene | FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation; Transcription factor involved in regulating gene activity following the primary growth factor response | 20.57 |
Nr4a1, nuclear receptor subfamily 4, group A, member 1 | The encoded protein acts as a nuclear transcription factor. Translocation of the protein from the nucleus to mitochondria induces apoptosis; May inhibit NF-kappa-B transactivation of IL2. Participates in energy homeostasis by sequestrating the kinase STK11 in the nucleus, thereby attenuating cytoplasmic AMPK activation. | 20.15 |
Ier2, immediate early response 2 | DNA-binding protein that seems to act as a transcription factor; Involved in the regulation of neuronal differentiation, acts upon JNK-signaling pathway activation and plays a role in neurite outgrowth in hippocampal cells. | 16.86 |
Sgk1, serum/glucocorticoid regulated kinase 1 | Encodes a serine/threonine protein kinase that plays an important role in cellular stress response. This kinase activates certain potassium, sodium, and chloride channels, suggesting an involvement in the regulation of processes such as cell survival, neuronal excitability, and renal sodium excretion. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. | 13.23 |
Cyr61, cystein rich protein 61 | Promotes cell proliferation, chemotaxis, angiogenesis and cell adhesion. Appears to play a role in wound healing by up-regulating, in skin fibroblasts, the expression of a number of genes involved in angiogenesis, inflammation and matrix remodeling including VEGA-A, VEGA-C, MMP1, MMP3, TIMP1, uPA, PAI-1 and integrins alpha-3 and alpha-5. CYR61-mediated gene regulation is dependent on heparin-binding. | 12.13 |
Vasn, vasorin | May act as an inhibitor of TGF-beta signaling. | 11.03 |
Sertad1, SERTA domain containing 1 | Stimulates E2F1/TFDP1 transcriptional activity. Renders the activity of cyclin D1/CDK4 resistant to the inhibitory effects of CDKN2A/p16INK4A. | 10.33 |
Gene | Function | Gnidilatidin (vs. Control) |
---|---|---|
Id2, inhibitor of DNA binding 2 | Promotes tumor cell migration and invasion; The protein ID2 belongs to the inhibitor of DNA binding family, members of which are transcriptional regulators that contain a helix-loophelix (HLH) domain but not a basic domain. | 0.16 |
Sytl2, synaptogaminlike 2 | The SLP homology domain (SHD) of this protein has been shown to specifically bind the GTPbound form of Ras-related protein Rab-27A (RAB27A). This protein plays a role in RAB27Adependent vesicle trafficking and controls melanosome distribution in the cell periphery. | 0.17 |
Tbca, tubulin cofactor a | Tubulin-folding protein; involved in the early step of the tubulin folding pathway.; The product of this gene is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. | 0.19 |
Sorbs1, Sorbin and SH3 domaincontaining 1 | This gene encodes a CBL-associated protein which functions in the signaling and stimulation of insulin. Mutations in this gene may be associated with human disorders of insulin resistance. Required for insulin-stimulated glucose transport. Involved in formation of actin stress fibers and focal adhesions (By similarity). | 0.21 |
Zfp85-rs1, Zinc finger protein 85, related sequence 1 | Regulation of transcription, DNA-templated; nucleic acid binding; metal ion binding; transcription corepressor activity | 0.21 |
Esco2, Establishment Of Sister Chromatid Cohesion NAcetyltransferase 2establishment of cohesion 1 homolog 2 | Acetyltransferase required for the establishment of sister chromatid cohesion. Couples the processes of cohesion and DNA eplication to ensure that only sister chromatids become paired together. In contrast to the structural cohesins, the deposition and establishment factors are required only during the S phase. Acetylates the cohesin component SMC3. | 0.22 |
Mtss1, metastasis suppressor 1 | May be related to cancer progression or tumor metastasis in a variety of organ sites, most likely through an interaction with the actin cytoskeleton. | 023 |
Zfp60, zinc finger protein 60 | Negative regulator of cartilage differentiation | 0.25 |
Psg28, pregnancyspecific glycoprotein 28 | Relevant for cell adhesion and for positive regulation of endocytosis, phagocytosis, and inflammatory response | 0.26 |
Brca1, breast cancer 1 | E3 ubiquitin-protein ligase that specifically mediates the formation of Lys-6-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. Required for appropriate cell cycle arrests after ionizing irradiation in both the Sphase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. | 0.27 |