Immunomodulatory and antitumor effects of shilajit and glycine: Natural metabolic modulators targeting breast and liver cancer

Table 1 Mechanistic overview of shilajit in cancer

Mechanism	Molecular target/pathway	Preclinical evidence	Potential clinical relevance
Apoptosis induction	Caspase-3, Bax/Bcl-2	Shilajit extracts trigger apoptosis in breast and liver cancer cells	Enhances cytotoxicity, tumor selectivity
ROS modulation	Mitochondria, glutathione	Increased ROS in malignant cells, reduced oxidative stress in normal cells	Tumor-specific redox modulation
Anti-angiogenesis	VEGF, endothelial proliferation	Inhibition of angiogenesis in vitro	Prevents tumor vascularization
NF-κB suppression	NF-κB p65 subunit	Reduced transcription of IL-6, TNF-α	Immunomodulation, sensitization to ICIs
Immunomodulation	Macrophages, antibodies	Bidirectional immune regulation	May reduce therapy toxicity, enhance immunity

Bax: B-cell lymphoma/Leukemia-2 family-associated X protein; Bcl-2: B-cell lymphoma/Leukemia-2 family; NF-κB: Nuclear factor-kappa B; VEGF: Vascular endothelial growth factor; ROS: Reactive oxygen species; TNF: Tumor necrosis factor; IL: Interleukin; ICI: Immune checkpoint inhibitor.

Table 2 Roles of glycine in cancer biology

Role	Pathway/target	Evidence	Implication
Metabolic substrate	One-carbon metabolism (SHMT, GLDC)	Supports nucleotide synthesis and methylation	Tumor proliferation, metabolic vulnerability
Redox defense	Glutathione synthesis	Maintains antioxidant pools	Protects normal cells; tumor paradox
Immunomodulation	Glycine receptor, NF-κB	Suppresses IL-6/IL-8, reduces inflammation	Mitigates therapy-induced toxicity
Tissue protection	Anti-fibrosis, ischemia-reperfusion	Prevents fibrosis, protects the liver/kidney	Beneficial in HCC and comorbidities
Tumor suppression	Anti-angiogenesis, apoptosis	Reduced metastasis in breast cancer models	Adjuvant potential

SHMT: Serine hydroxymethyltransferase; GLDC: Glycine decarboxylase; NF-κB: Nuclear factor-kappa B; HCC: Hepatocellular carcinoma; IL: Interleukin.