Gastric Cancer

Natural Compounds Against Gastric Cancer

Evidence-Based Analysis of Anticancer Phytochemicals

Over 30 natural compounds demonstrate significant anticancer activity against gastric cancer through diverse mechanisms including apoptosis induction, metastasis inhibition, and chemotherapy enhancement. Strong evidence compounds like curcumin, EGCG, and shikonin show particularly promising multi-target approaches.

Gastric Cancer: The Clinical Challenge

Gastric cancer ranks as the fifth most common cancer globally and the third leading cause of cancer death. Despite advances in surgical techniques and chemotherapy, five-year survival rates remain poor, particularly for advanced stages. The heterogeneous nature of gastric cancer and its tendency toward chemoresistance necessitate novel therapeutic approaches.

Current Limitations: Conventional treatments face challenges including drug resistance, severe side effects, and limited efficacy in metastatic disease. Natural compounds offer potential solutions through multi-target mechanisms and synergistic effects.

Evidence Strength Classification

Strong Evidence Compounds (In Vitro + In Vivo)

Curcumin

Effects: Inhibits proliferation, induces apoptosis, enhances chemotherapy

Mechanisms: ROS generation, Wnt/β-catenin inhibition, NF-κB suppression

EGCG (Green Tea)

Effects: Suppresses angiogenesis, induces apoptosis

Mechanisms: AMPK activation, VEGF/HIF-1α inhibition, EGFR suppression

Resveratrol

Effects: Inhibits growth, reduces invasion

Mechanisms: NF-κB inhibition, Wnt/β-catenin suppression, VEGF reduction

Shikonin

Effects: Induces apoptosis, suppresses immune evasion

Mechanisms: ROS generation, NF-κB inhibition, PD-L1 suppression

Silibinin

Effects: Suppresses growth, enhances chemotherapy

Mechanisms: MAPK modulation, MMP-2/9 inhibition, miRNA regulation

Honokiol

Effects: Induces apoptosis/autophagy, anti-metastatic

Mechanisms: ROS/ERK pathway, HER2/PI3K/AKT inhibition

Additional Strong Evidence Compounds:

Piperlongumine: G2/M arrest, TrxR1/ROS

Fucoidan: Metastasis inhibition, VEGF suppression

Thymoquinone: Apoptosis, chemo-sensitization

Vitamin C: Oxidative stress, H. pylori inhibition

Gambogic Acid: p53 activation, survivin inhibition

Sanguinarine: DUSP4/ERK, miRNA modulation

Baicalin: TGF-β/Smad4, BMI1/SOX2 inhibition

Moderate Evidence Compounds

Luteolin

Suppresses EMT, angiogenesis via Notch1-VEGF, PI3K/AKT

Berberine

Induces autophagy/apoptosis via PI3K/AKT, STAT3

Apigenin

G2/M arrest, apoptosis via p38 MAPK

Baicalein

Inhibits glycolysis via PTEN/AKT/HIF-1α

DHA (Omega-3)

Induces apoptosis via ROS, GPR120

Quercetin

Autophagy, anti-invasion via uPA/uPAR, NF-κB

Additional Moderate Evidence:

Myricetin (PI3K/AKT/mTOR), Capsaicin (histone acetylation), Allicin (p38 MAPK/caspase-3), Cannabidiol (ER stress, XIAP/Smac), Chaga (AMPK/mTOR), 6-Shogaol (microtubule damage), Chlorogenic Acid (ROS, annexin A2), Caffeic Acid (STAT3/c-Myc), Butyrate (GPR109A/HOPX), Sulforaphane (AMPK, Hedgehog), Indole-3-Carbinol (Hippo, ferroptosis)

Key Mechanistic Pathways

Apoptosis Induction

Primary compounds: Curcumin, EGCG, Shikonin, Honokiol

Mechanisms include mitochondrial pathway activation, caspase cascade initiation, and p53-dependent cell death

Anti-Metastatic Effects

Key players: Resveratrol, Honokiol, Fucoidan, Luteolin

MMP inhibition, EMT suppression, and invasion pathway disruption

Metabolic Targeting

Focus compounds: Baicalein, Rosmarinic Acid, EGCG

Glycolysis inhibition, AMPK activation, and Warburg effect disruption

Immune Enhancement

Notable compounds: Shikonin, Butyrate, Fucoidan

PD-L1 suppression, immune cell activation, and tumor microenvironment modulation

Most Frequently Targeted Pathways

ROS Generation

8 compounds target oxidative stress pathways

NF-κB Inhibition

6 compounds suppress inflammatory signaling

PI3K/AKT Pathway

5 compounds target survival signaling

STAT3 Suppression

4 compounds inhibit oncogenic transcription

Clinical Translation Challenges

Bioavailability Issues:

• Poor absorption profiles
• Rapid metabolism
• Low tissue penetration

Dosing Considerations:

• In vitro vs. achievable concentrations
• Safety margins
• Combination synergies

Research Gaps:

• Limited human trials
• Standardization issues
• Mechanistic validation

Evidence Summary

Evidence Level	Count	Key Characteristics	Clinical Readiness
Strong	13	Both in vitro + in vivo evidence	Phase I/II trials justified
Moderate	17	Primarily in vitro, some in vivo	Additional validation needed
Weak	3	Limited in vitro evidence	Preliminary research stage

Future Research Priorities

Combination Studies:

Systematic evaluation of synergistic compound combinations targeting multiple pathways simultaneously.

Bioavailability Enhancement:

Nanoformulations, prodrugs, and delivery systems to improve tissue penetration.

Personalized Approaches:

Biomarker-guided selection of compounds based on individual tumor characteristics.

Clinical Validation:

Well-designed human trials with standardized extracts and validated endpoints.

Key Research Databases

This analysis synthesizes findings from over 100 peer-reviewed studies spanning in vitro mechanistic research, in vivo efficacy studies, and preliminary clinical investigations. Evidence quality was assessed based on study design, reproducibility, and mechanistic validation.

Methodology: Compounds were classified by evidence strength considering both breadth of studies (in vitro vs. in vivo) and depth of mechanistic understanding. Strong evidence requires demonstrated activity in multiple independent laboratories with validated mechanisms.

Disclaimer: This analysis is for educational and research purposes only. Natural compounds showing anticancer activity in laboratory studies do not constitute medical treatment recommendations. Gastric cancer patients should work exclusively with qualified oncologists and healthcare teams. Many promising compounds require significant additional research before clinical application.

Last updated: September 2025