| Features: |
| Honokiol is a Lignan isolated from bark, seed cones and leaves of trees of Magnolia species. Honokiol was traditionally used for anxiety and stroke treatment, as well as the alleviation of flu symptoms. -considered to have antioxidant properties -low oral bioavailability and difficulty in intravenous administration -the development of various formulations of honokiol, including microemulsion, liposomes, nanoparticles and micelle copolymers have successfully solved the problem of low water solubility. Pathways: -Inhibit NF-κB activation -Downregulate STAT3 signalin -Inhibiting the PI3K/Akt pathway, -Inhibition of mTOR -Influences various MAPK cascades—including ERK, JNK, and p38 -Inhibition of EGFR -Inhibiting Notch pathway (CSCs) -GPx4 inhibit -Can induce ER stress in cancer cells, which contributes to the activation of unfolded protein response (UPR) pathways -Disrupt the mitochondrial membrane potential in cancer cells. -Reported to increase ROS production in cancer cells -Can exhibit antioxidant properties in normal cells. - has some inhibitor activity but Not classified as HDAC inhibitor as weaker and may work more indirectly. - is well-known in the research community for its role in activating SIRT3 -Note half-life 40–60 minutes BioAv Pathways: - induce ROS production in cancer cells, and typically lowers ROS in normal cells - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓ Prx - Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑, - lowers Inflammation : NF-kB↓, COX2↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, - inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, VEGF↓, ROCK1↓, RhoA↓, NF-κB↓, CXCR4↓, ERK↓ - reactivate genes thereby inhibiting cancer cell growth : HDAC↓, EZH2↓, P53↑, HSP↓, - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, ERK↓, EMT↓, - inhibits glycolysis and ATP depletion : HIF-1α↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, GlucoseCon↓ - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, Notch↓, EGFR↓, - inhibits Cancer Stem Cells : CSC↓, CD133↓, β-catenin↓, sox2↓, nestin↓, OCT4↓, - Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK, ERK↓, JNK, TrxR**, - Shown to modulate the nuclear translocation of SREBP-2 (related to cholesterol). - Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective, - Selectivity: Cancer Cells vs Normal Cells |
| Source: |
| Type: |
| Cancer Stem Cells Phytochemicals (natural plant-derived compounds) that may affect CSCs: Curcumin — suppresses self-renewal and pathways (Wnt/Notch/Hedgehog). Resveratrol — shown to reduce CSC populations and sphere formation in multiple models. Sulforaphane (from broccoli sprouts) — reported to inhibit CSC properties and pathways; active in vitro and in vivo. EGCG (epigallocatechin-3-gallate, green tea) — reduces CSC markers and sphere formation in several cancer types. Quercetin — reported to inhibit CSC proliferation, self-renewal and invasiveness (breast, endometrial, others). Berberine — shown to suppress CSC “stemness” and reduce tumorigenic properties in multiple models. Genistein (soy isoflavone) — decreases CSC markers, sphere formation and stemness signaling in prostate/breast/other models. Honokiol (Magnolia bark) — shown to eliminate or suppress CSC-like populations in oral, colon, glioma models. Luteolin — inhibits stemness/EMT and reduces CSC markers and self-renewal in breast, prostate and other models. Withaferin A (from Withania somnifera / ashwagandha) — multiple preclinical reports show WA targets CSCs and reduces tumor growth/metastasis in models. Circadian disruption in cancer and regulation of cancer stem cells by circadian clock genes: An updated review Potential Role of the Circadian Clock in the Regulation of Cancer Stem Cells and Cancer Therapy Can we utilise the circadian clock to target cancer stem cells? |
| 4659- | HNK, | Honokiol Eliminates Human Oral Cancer Stem-Like Cells Accompanied with Suppression of Wnt/β-Catenin Signaling and Apoptosis Induction |
| - | in-vitro, | Oral, | NA |
| 4688- | HNK, | Honokiol Suppresses Renal Cancer Cells’ Metastasis via Dual-Blocking Epithelial-Mesenchymal Transition and Cancer Stem Cell Properties through Modulating miR-141/ZEB2 Signaling |
| - | vitro+vivo, | RCC, | A498 |
| 1120- | HNK, | Honokiol suppresses renal cancer cells' metastasis via dual-blocking epithelial-mesenchymal transition and cancer stem cell properties through modulating miR-141/ZEB2 signaling |
| - | vitro+vivo, | RCC, | NA |
| 2864- | HNK, | Honokiol: A Review of Its Anticancer Potential and Mechanisms |
| - | Review, | Var, | NA |
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