Database Query Results : Orlistat, ,

OLST, Orlistat: Click to Expand ⟱
Features:

Orlistat (tetrahydrolipstatin; anti-obesity drug; OTC 60 mg, Rx 120 mg). A potent, minimally absorbed gastrointestinal lipase inhibitor that reduces dietary fat absorption (~30% at 120 mg TID).

Primary mechanisms (conceptual rank):
1) Irreversible inhibition of gastric + pancreatic lipases (↓ triglyceride hydrolysis)
2) ↓ Chylomicron formation → ↓ systemic lipid flux
3) Secondary metabolic shifts (weight loss–mediated insulin sensitivity changes)

Bioavailability / PK relevance: Very low systemic absorption (<1%); primary action is intraluminal in gut. Most systemic mechanistic cancer data derive from higher in-vitro concentrations or off-target effects (e.g., FASN inhibition).

In-vitro vs oral exposure: Many anti-cancer studies use concentrations likely exceeding achievable plasma levels from standard dosing (qualifier: high concentration only for direct tumor cytotoxicity).

Clinical evidence status: Approved for obesity; cancer evidence largely preclinical/observational; no robust oncology RCT indication.

Inhibits lipase and is used to facilitate weight loss.

Orlistat — Cancer vs Normal Cell Pathway Map

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Fatty Acid Synthase (FASN) ↓ (high concentration only) ↔ (low FASN dependence) R/G Lipid synthesis blockade; apoptosis Well-known off-target in vitro; many tumors overexpress FASN. Clinical relevance limited by low systemic exposure.
2 Lipid availability / metabolic flux ↓ (indirect) ↓ (systemic) G Reduced lipid supply Weight-loss–mediated effect; may indirectly reduce pro-tumor metabolic signaling (insulin/IGF axis).
3 PI3K/AKT/mTOR ↓ (model-dependent) ↔ / ↓ (metabolic improvement) R/G Reduced anabolic signaling Often secondary to lipid stress or metabolic shifts; not primary gut mechanism.
4 Apoptosis (caspase activation) ↑ (high concentration only) ↔ R/G Programmed cell death Observed in cancer lines at supra-physiologic levels; translation uncertain.
5 ROS / lipid peroxidation stress ↑ (lipid stress–related; model-dependent) ↔ P/R Metabolic oxidative stress Linked to FASN inhibition; not central to approved mechanism.
6 NRF2 axis ↔ (insufficient evidence) ↔ R/G Not a dominant axis No consistent evidence of primary NRF2 modulation at therapeutic exposure.
7 Ferroptosis (lipid metabolism link) ↑ (theoretical / model-dependent) ↔ R/G Lipid vulnerability shift FASN inhibition could alter lipid composition; ferroptosis relevance remains investigational.
8 HIF-1α / Warburg coupling ↓ (indirect; metabolic improvement) ↔ G Reduced pro-growth metabolic signaling Likely secondary to weight loss and insulin reduction rather than direct tumor action.
9 Ca²⁺ signaling ↔ ↔ P/R No primary role Not a recognized mechanistic axis for orlistat.
10 Clinical Translation Constraint ↓ (constraint) ↓ (constraint) — Minimal systemic exposure Low absorption limits direct anti-tumor applicability; GI side effects and fat-soluble vitamin malabsorption noted.

TSF legend: P: 0–30 min; R: 30 min–3 hr; G: >3 hr
Scientific Papers found: Click to Expand⟱
1637- HCA,  OLST,    Orlistat and Hydroxycitrate Ameliorate Colon Cancer in Rats: The Impact of Inflammatory Mediators
- in-vivo, Colon, NA
TumVol↓, OS↑, *IL6↓, *NF-kB↓, *eff↑, *Casp3↓, *TNF-α↓, *Catalase↑, *NO↓, *ROS↓, *Inflam↓, *Apoptosis↓,
969- OLST,    Orlistat as a FASN inhibitor and multitargeted agent for cancer therapy
- Review, NA, NA
FASN↓,
1045- OLST,    Fatty acid synthase inhibitor orlistat impairs cell growth and down-regulates PD-L1 expression of a human T-cell leukemia line
- in-vitro, AML, Jurkat
FASN↓, TumCG↓, PD-L1↓,
1225- OLST,    Orlistat Induces Ferroptosis in Pancreatic Neuroendocrine Tumors by Inactivating the MAPK Pathway
- vitro+vivo, PC, NA
TumCMig↓, TumCI↓, Ferroptosis↑, MAPK↓,
1226- OLST,    Knockdown of PGM1 enhances anticancer effects of orlistat in gastric cancer under glucose deprivation
- vitro+vivo, GC, NA
PGM1∅, FASN↓, Apoptosis↑, lipidLev↑, GlucoseCon↑, eff↑,
1227- OLST,    Anti-Obesity Drug Orlistat Alleviates Western-Diet-Driven Colitis-Associated Colon Cancer via Inhibition of STAT3 and NF-κB-Mediated Signaling
- in-vivo, CRC, NA
OS↑, Inflam↓, TumCG↓, STAT3↓, NF-kB↓, β-catenin/ZEB1↓, Slug↓, XIAP↓, CDK4↓, cycD1/CCND1↓, Bcl-2↓,
1228- OLST,    Orlistat Mitigates Oxidative Stress-Linked Myocardial Damage via NF-κβ- and Caspase-Dependent Activities in Obese Rats
- in-vivo, Obesity, NA
*ROS↓, *NF-kB↓,
1251- RT,  OLST,    Rutin and orlistat produce antitumor effects via antioxidant and apoptotic actions
- in-vitro, BC, MCF-7 - in-vitro, PC, PANC1 - in-vivo, NA, NA
TumVol↓, *CEA↓, *FASN↓, *ROS↓, *MDA↓, *GSH↑, Apoptosis↑,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↑, 1,  

Mitochondria & Bioenergetics ⓘ

XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

FASN↓, 3,   GlucoseCon↑, 1,   lipidLev↑, 1,   PGM1∅, 1,  

Cell Death ⓘ

Apoptosis↑, 2,   Bcl-2↓, 1,   Ferroptosis↑, 1,   MAPK↓, 1,  

Cell Cycle & Senescence ⓘ

CDK4↓, 1,   cycD1/CCND1↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

STAT3↓, 1,   TumCG↓, 2,  

Migration ⓘ

Slug↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   β-catenin/ZEB1↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,   NF-kB↓, 1,   PD-L1↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Clinical Biomarkers ⓘ

PD-L1↓, 1,  

Functional Outcomes ⓘ

OS↑, 2,   TumVol↓, 2,  
Total Targets: 25

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

Catalase↑, 1,   GSH↑, 1,   MDA↓, 1,   ROS↓, 3,  

Core Metabolism/Glycolysis ⓘ

FASN↓, 1,  

Cell Death ⓘ

Apoptosis↓, 1,   Casp3↓, 1,  

Migration ⓘ

CEA↓, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL6↓, 1,   Inflam↓, 1,   NF-kB↓, 2,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Clinical Biomarkers ⓘ

CEA↓, 1,   IL6↓, 1,  
Total Targets: 16

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#:14  Target#:%  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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