Table 2.
Summary of RSV impact on cancer stem cell signaling pathways reported.
| Signaling Pathway | Experimental Model Systems | RSV Effects | Ref. |
|---|---|---|---|
| Notch signaling | Glioblastoma cell lines (A172 and T98G) | Notch-1 activation ↑ dependent p53 mediated anti-proliferative and pro-apoptotic effects | Lin et al. (2011) |
| Human GI carcinoid tumor cell lines (BON); Human pulmonary carcinoid cell lines (NC–H727) | Growth ↓ through S-phase cell cycle arrest Expression of neuroendocrine (NE) peptides/hormones chromogranin A and serotonin through activation of the Notch-2 isoform ↑ |
Pinchot et al. (2011) | |
| Anaplastic Thyroid Carcinoma (ATC) Cell Lines (HTh7 and 8505C) | Dose-dependent inhibited ATC growth ↓ Cell differentiation ↑ via activation of Notch-1 signaling ↑ |
Yu et al. (2013) | |
| Wnt signaling | Colorectal cancer cell lines (LoVo cells) | Dose-dependent inhibition of the nuclear localization of β-catenin ↓ c-Myc and MMP-7 ↓ Cell proliferation and invasion ↓ These effects of RSV are opposite to that of the long non-coding RNA-MALAT1 cell proliferation and invasion abilities |
Ji et al. (2013) |
| Human normal breast epithelial cell line (MCF10A) and breast cancer cell line (MCF-7, SUM159) | Wnt/β-catenin pathway proteins ↓ β-catenin ↑ markedly reduced RSV-induced cytotoxicity and autophagy |
Fu et al. (2014) | |
| Human normal (CCD112CoN) and colorectal cancer cell lines (HCT116, SW480, LoVo and CaCo-2) | TCF4 transcription factor expression ↓ via wnt/β-catenin pathway Phosphorylation of TCF4 ↑via ERK and P38 dependent pathways Apoptosis ↑ |
Jeong et al. (2015) | |
| Glioblastoma patient derived stem cells (GBM2, GBM7, G144, G179, G166, GliNS2, GBM04) | Wnt and EMT activator mediated GSC cell proliferation ↓ Cell mortality ↑ Cell motility↑ |
Cilibrasi et al. (2017) | |
| Squamous cell carcinoma cell line (Colo 16 cells) | RSV (100 μM) exhibited Wnt ↓ leading to Cell growth ↓ Apoptosis ↑ Transfection with β-catenin-specific siRNA enhanced RSV susceptibility |
Liu et al. (2017) | |
| GC-MSCs derived from the gastric adenocarcinoma patient tissues | RSV reversed the progress of EMT Metastasis ↓ Wnt/β-catenin pathway proteins ↓ |
Yin et al. (2020) | |
| SHH signaling (Sonic Hedgehog Pathway) | Chronic myeloid leukemia cells (K562 cells) | RSV acted as Bcr-Abl inhibitor SHH pathway proteins ↓ patched (PTCH) ↓ Smoothened (Smo) ↓ Gli-1 ↓ Viability of CML cells ↓ |
Liao et al. (2012) |
| Acute Myeloid Leukemia (AML) patient derived mononuclear cells (MNCs). | RSV blocked IL-6 stimulated growth of AML cells through SHH signaling | Su et al. (2013) | |
| Human colorectal cancer cell lines (HCT116 cells) | Cell viability and migration ↓ Apoptosis ↑ SHH pathway proteins ↓ |
Du et al. (2016) | |
| Renal cancer stem cells (ACHN and 786-O cells) | Size and number of tumorspheres ↓ via SHH signaling While purmorphamine up regulated SHH pathway and weakened the RSV effects |
Sun et al. (2020) | |
| PI3K Signaling | Human colon cancer cells (HCT116 cells) | Anti-proliferative effects ↑ via PTEN/PI3K/Akt and Wnt/β-catenin pathway protein regulation | Liu et al. (2014) |
| Glioblastoma patient derived Glioblastoma-initiating cells (GICs) | Invasion and migration of GICs ↓ via suppressing PI3K/Akt/NF-κB and MMP-2 expression ↓ | Jiao et al. (2015) | |
| Adriamycin resistant chronic myeloid leukemia cell line (K562/Adr) | Anti-proliferative activities of bestatin ↑ P-gp expression ↓ via PI3K/Akt/mTOR signaling pathway | Wang et al. (2016) | |
| Human colorectal cancer cell lines (HCT116 cells) | Anti-cancer activity ↑ PI3K/AKT signaling ↓ BMP7 ↑ Phosphorylation of Akt1/2/3 and PTEN ↑ |
Zeng et al. (2017) | |
| Human promyelocytic leukemia cells (HL-60) and ADR (Adriamycin)-resistant cell line (HL-60/ADR) | Drug resistance ↓ via PI3K/AKT/Nrf2 signaling and MRP1 expression | Li et al. (2019) | |
| Human acute promyelocytic leukemia cell lines (NB-4 and HL-60 cells) | PTEN expression ↑ PI3K/AKT pathway proteins ↓ Cell proliferation ↓ Apoptosis ↑ |
Meng et al. (2019) | |
| Human small-cell lung cancer cell lines (H446 cells) | Cell viability ↓ and apoptosis ↑via PI3K/Akt/c-Myc pathway | Li et al. (2020) | |
| Human papillary thyroid cancer cell lines (KTC-1 and TPC-1 cells); Mouse xenograft models | Anti-tumor effects ↑of rapamycin mediated by PI3K/AKT/mTOR pathway | Bian et al. (2020) | |
| Murine melanoma cell line (B16–F10), human melanoma cell line (A375) | AKT/mTOR pathway proteins ↓ Autophagy ↑ Growth, viability and migration ↓ |
Gong et al. (2020) | |
| TGF/SMAD Signaling | Human epidermoid carcinoma cell lines (A431) and mouse models | Ultraviolet B (UVB) induced malignant tumor progression ↓ in p53+/−/SKH-1 mice through Akt mediated TGF-β2 ↓ | Kim et al. (2011) |
| Colorectal cancer cell lines (LoVo cells) | Epithelial to mesenchymal transition (EMT) ↓ TGF-β1/SMAD signaling pathway ↓ |
Ji et al. (2015) | |
| Human breast cancer cell lines (MDA-MB-231) and xenograft mouse model | Migration and metastasis ↓ by reversing TGF-β1 induced EMT | Sun et al. (2019) | |
| Human glioblastoma multiforme cell lines (LN18, U87 cells) | EMT ↓ EMT-generated stem cell like properties ↓ via Smad-dependent signaling regulation |
Song et al. (2019) | |
| NF-κB Signaling | Human multiple myeloma cell lines (U266), Patient derived MM.1 or MM.1S cells | Constitutive and IL-6 induced activation of STAT3 ↓ Constitutive activation of NF-κB ↓ Cell proliferation ↓ Sensitization of bortezomib and thalidomide mediated apoptosis ↑ |
Bharadwaj et al. (2007) |
| PPAR pathway | Human colon carcinoma cell lines (SW480, HCT116, Caco2 and SW620) | Apoptosis ↑ Cell proliferation ↓ in combination with PPARγ |
Aires et al. (2014) |
| Bovine arterial endothelial cells (BAECs) and PPARα knockout mice | RSV exerted agonistic activity of PPARα as its direct target mediating long term effects of RSV under in vivo conditions | Takizawa et al. (2015) | |
| JAK/STAT Pathway | Medulloblastoma cell lines (UW228-2 and UW228-3 Cells) | Bcl-2 expression ↑ STAT3 ↓ Survivin, cyclin D1, Cox-2 and c-Myc ↓ Growth suppression ↑ Differentiation-like changes ↑ |
Yu et al. (2008) |
| Human osteosarcoma cell lines (MNNG/HOS, MG-63 cells), osteoblast cell line (hFOB1.19 cells) | Cell proliferation and tumorigenesis ↓ correlated with cytokines inhibition related JAK2/STAT3 signaling blockage | Peng et al. (2018) | |
| Human ovarian cancer cell lines (SKOV3, Caov-3, OVCAR-4 and OVCAR-8 Cells) | RSV analog – pterostilbene exhibited anti-tumor activity via anti-proliferative and pro-apoptotic mechanisms through JAK/STAT3 pathway ↓ | Wen et al. (2018) |