lambertianic acid / SREBP1/SREBF1 Cancer Research Results

lamb, lambertianic acid: Click to Expand ⟱
Features:

Lambertianic acid — a naturally occurring labdane-type diterpenoid carboxylic acid found in several conifer species, particularly Pinus koraiensis, Pinus lambertiana, and Platycladus orientalis. It is an experimental natural-product small molecule rather than an approved drug. The abbreviation LA is commonly used in the scientific literature, although the Nestronics product abbreviation is lamb. Lambertianic acid has reported anticancer, anti-inflammatory, anti-allergic, metabolic, and muscle-protective activities, but its therapeutic evidence remains predominantly cellular and preclinical. Its anticancer activity appears strongly context-dependent and involves coordinated effects on oxidative stress, AMPK signaling, cancer metabolism, STAT3/NF-κB survival signaling, androgen receptor signaling, and apoptosis.

Primary mechanisms (ranked):

  1. ↑ ROS with ROS-dependent activation of LKB1/AMPK/ACC signaling, producing metabolic stress and apoptosis in susceptible cancer cells.
  2. ↓ PKM2/HK2/LDHA-driven glycolysis and ↓ PKM2/β-catenin signaling, producing an anti-Warburg metabolic effect.
  3. ↓ STAT3 and NF-κB signaling, including ↓ STAT3 phosphorylation, ↓ RelA/p65 activation/acetylation, and suppression of downstream survival and inflammatory proteins.
  4. ↑ intrinsic and extrinsic apoptosis through caspase activation, PARP cleavage, ↓ BCL-2/BCL-xL/XIAP/survivin, and context-dependent ↑ DR4/TRAIL sensitivity.
  5. ↑ AMPK with ↓ AKT/mTOR and ↓ FOXM1 signaling, contributing to growth arrest and apoptosis.
  6. ↓ androgen receptor signaling in androgen-responsive prostate cancer, with ↓ AR nuclear signaling and ↓ PSA.
  7. Cell-cycle inhibition through ↓ cyclin D1/CDK4/CDK6 or ↓ cyclin B1 and context-dependent ↑ p53/p21/p27.

Bioavailability / PK relevance: Human pharmacokinetic parameters, oral bioavailability, plasma half-life, distribution, metabolism, and clinically achievable concentrations have not been adequately established. Lambertianic acid is a lipophilic diterpenoid and should therefore not be assumed to achieve the micromolar exposures used in cell-culture studies after ordinary dietary or oral exposure. No validated therapeutic dosing regimen exists.

In-vitro vs systemic exposure relevance: Most anticancer experiments use approximately 10–200 µM lambertianic acid, depending on the model. Some signaling effects occur around 15–30 µM, whereas androgen-receptor prostate-cancer experiments used substantially higher concentrations, including approximately 100–200 µM. There is currently insufficient human PK evidence to demonstrate that these concentrations are systemically achievable. Normal-cell selectivity is also incompletely characterized; recent C2C12 studies found little cytotoxicity at 12.5–25 µM but measurable loss of viability at 50–100 µM.

Clinical evidence status: Preclinical. Evidence consists primarily of cultured cancer cells with limited animal-supporting evidence from non-cancer metabolic studies. No established randomized clinical trial evidence, approved oncologic indication, validated human anticancer dose, or regulatory approval for lambertianic acid as a therapeutic agent was identified.

Lambertianic Acid Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 ROS-LKB1-AMPK-ACC metabolic stress ROS ↑; LKB1 ↑; AMPK ↑; ACC phosphorylation ↑ Not established G Apoptosis and metabolic stress ↑ ROS scavenging with NAC substantially reverses several anticancer effects, supporting ROS as a mechanistically important upstream event rather than merely a secondary marker.
2 Glycolysis and PKM2-beta-catenin axis PKM2 ↓; p-PKM2 ↓; HK2 ↓; LDHA ↓; lactate production ↓; beta-catenin ↓; glycolysis ↓ Not established G Warburg metabolism ↓; apoptosis ↑ Particularly demonstrated in DU145 and PC3 prostate cancer cells. ROS contributes upstream to suppression of PKM2 and associated metabolic signaling.
3 STAT3-NF-kB-p300-RelA survival signaling p-STAT3 ↓; NF-kB activation ↓; p300 ↓; RelA acetylation ↓; nuclear translocation ↓ Not established G Survival and inflammatory signaling ↓ Associated with ↓ XIAP, survivin, BCL-2, BCL-xL, VEGF, COX-2, c-Myc, IL-6 and TNF-alpha. miR-134 ↑ appears to participate in this pathway.
4 Intrinsic apoptosis Caspase-3 ↑; caspase-9 ↑; PARP cleavage ↑; BAX ↑; BCL-2 ↓ Not adequately established G Apoptosis ↑ Observed across prostate, hepatocellular, breast and lung cancer models. Apoptotic response is frequently downstream of AMPK activation and suppression of survival signaling.
5 AMPK-AKT-mTOR-FOXM1 axis AMPK ↑; AKT ↓; mTOR ↓; FOXM1 ↓; cyclin B1 ↓ AMPK modulation reported in non-cancer metabolic models G Proliferation ↓; apoptosis ↑ AMPK inhibition reverses several lambertianic-acid effects, supporting a functional rather than merely correlative role for AMPK.
6 Androgen receptor signaling AR ↓; AR nuclear translocation ↓; PSA ↓ Not established G Androgen-dependent proliferation ↓ Best demonstrated in LNCaP prostate cancer cells. Relatively high concentrations were required compared with several later mechanistic studies.
7 Cell-cycle regulation Cyclin D1 ↓; CDK4 ↓; CDK6 ↓; p53 ↑; p21 ↑; p27 ↑; cyclin B1 ↓ Not established G G1 or G2/M arrest ↑ (model-dependent) Cell-cycle phenotype varies by cancer model. LNCaP cells predominantly demonstrate G1 arrest, whereas breast-cancer studies report G2/M-associated effects.
8 TRAIL death-receptor sensitization DR4 ↑; caspase-8 ↑; Bid activation ↑; XIAP ↓; FLIP ↓; NF-kB ↓ Not established G TRAIL-induced apoptosis ↑ Lambertianic acid sensitized A549 and H1299 non-small-cell lung cancer cells to TRAIL. This is a combination-dependent chemosensitization-like mechanism rather than evidence of clinical combination efficacy.
9 Angiogenic and inflammatory survival factors VEGF ↓; COX-2 ↓; IL-6 ↓; TNF-alpha ↓ COX-2, IL-6, PGD2 and LTC4 ↓ in activated mast-cell models G Inflammatory and pro-survival signaling ↓ These effects overlap substantially with suppression of STAT3 and NF-kB and are therefore best considered downstream or secondary mechanisms.
10 Clinical Translation Constraint Effective concentrations commonly in micromolar range Normal-cell therapeutic window incompletely defined G Clinical applicability uncertain Human PK, oral bioavailability, dose-limiting toxicity, target exposure, long-term safety and anticancer efficacy have not been established. Current evidence does not justify assuming that experimental concentrations are achievable in humans.

P: 0–30 min    R: 30 min–3 hr    G: >3 hr
SREBP1/SREBF1, sterol regulatory element-binding protein 1: Click to Expand ⟱
Source:
Type:
SREBP1 is a key transcription factor that regulates genes involved in fatty acid and triglyceride synthesis. It primarily governs lipid metabolism by controlling the expression of enzymes required for de novo lipogenesis, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC), among others.
Two main isoforms—SREBP1a and SREBP1c—with SREBP1c being more involved in the regulation of lipogenesis in metabolic tissues.

Many cancers display elevated levels of SREBP1 activity. Increased expression or activation of SREBP1 supports the metabolic reprogramming that is characteristic of cancer cells, enabling them to meet the enhanced lipid requirements for membrane synthesis and energy storage during rapid cell proliferation.
Elevated SREBP1 activity is often linked to more aggressive cancer phenotypes. High SREBP1 levels can drive rapid proliferation, metastasis, and resistance to certain therapies, thereby correlating with poorer clinical outcomes in several cancers.

SREBF1 - Sterol Regulatory Element-Binding Transcription Factor 1 / SREBP-1

Abbreviation: SREBF1, SREBP-1, SREBP1

Type: Lipogenic transcription factor / basic helix-loop-helix leucine zipper transcription factor

Function: SREBF1 encodes SREBP-1, a master regulator of fatty-acid synthesis, lipid homeostasis, and metabolic gene expression. SREBP-1 is synthesized as an inactive endoplasmic-reticulum membrane precursor and, following SCAP-dependent processing and proteolytic cleavage, its active N-terminal transcription factor enters the nucleus. SREBP-1 regulates genes involved in de novo lipogenesis including FASN, ACACA/ACC, SCD1, and ACLY. The SREBF1 gene produces the SREBP-1a and SREBP-1c isoforms.

Cancer: ↑ Frequently increased or activated in cancer. Elevated SREBP-1 promotes de novo fatty-acid synthesis and metabolic reprogramming required for rapid tumor-cell proliferation. SREBP-1 can also promote survival, epithelial-mesenchymal transition, invasion, metastasis, tumor-microenvironment adaptation, ferroptosis resistance, and resistance to chemotherapy and radiotherapy. Genetic or pharmacological inhibition of SREBP-1 suppresses tumor growth in multiple preclinical cancer models.
Scientific Papers found: Click to Expand⟱
8155- lamb,    Ethanol extract of Pinus koraiensis leaves containing lambertianic acid exerts anti-obesity and hypolipidemic effects by activating adenosine monophosphate-activated protein kinase (AMPK)
- vitro+vivo, Nor, 3T3
*p‑AMPK↑, *PPARγ↓, *CEBPA↓, *adiP↓, *Fas↓, *SREBP1/SREBF1↓, *HMGCR↓, *lipidLev↓, *TG/TAG↓, *Weight↓, *LDL↓, *Obesity↓,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


Core Metabolism/Glycolysis(tgid=4) ⓘ

adiP↓, 1,   p‑AMPK↑, 1,   LDL↓, 1,   lipidLev↓, 1,   PPARγ↓, 1,   SREBP1/SREBF1↓, 1,  

Cell Death(tgid=5) ⓘ

Fas↓, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

CEBPA↓, 1,   HMGCR↓, 1,  

Clinical Biomarkers(tgid=22) ⓘ

TG/TAG↓, 1,  

Functional Outcomes(tgid=23) ⓘ

Obesity↓, 1,   Weight↓, 1,  
Total Targets: 12

Scientific Paper Hit Count for: SREBP1/SREBF1, sterol regulatory element-binding protein 1
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:315  Target#:1034  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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