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Betulinic Acid in Gastrointestinal Cancers: Mechanistic Prioritization, Nano-Enabled Delivery, and Translational

Ajay Kumar1, Amita2, Brahmjot Singh3

  • 1Department of Environmental Science, Graphic Era (Deemed to Be University), Dehradun, Uttarakhand, India.

Molecular Nutrition & Food Research
|June 18, 2026
PubMed

Insights

Betulinic acid (BA) shows promise as a natural anticancer agent for gastrointestinal (GI) cancers by targeting key pathways and reversing resistance. Further research and nano-delivery optimization are needed for clinical application.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Gastrointestinal (GI) cancers are a leading cause of mortality worldwide, often diagnosed late and developing chemotherapy resistance.
  • Tumor genetic alterations drive metabolic, inflammatory, and immune evasion mechanisms, necessitating novel therapeutic strategies.
  • Current systemic therapies offer limited sustained responses in progressive GI disease.

Purpose of the Study:

  • To evaluate the potential of betulinic acid (BA) as a targeted therapeutic agent for GI cancers.
  • To explore the mechanisms of action of BA, including its effects on apoptosis, signaling pathways, and cancer stemness.
  • To identify challenges and opportunities for the clinical translation of BA, particularly concerning its delivery and formulation.

Main Methods:

  • Review of preclinical data on betulinic acid's efficacy in various GI cancer models.
  • Analysis of BA's molecular targets, including mitochondrial apoptosis, PI3K/Akt, NF-κB pathways, epithelial-mesenchymal transition, and cancer stemness.
  • Assessment of nano-delivery strategies for improving BA's solubility and bioavailability.

Main Results:

  • Betulinic acid demonstrates anticancer activity by inducing mitochondrial apoptosis and inhibiting critical oncogenic pathways (PI3K/Akt, NF-κB).
  • BA effectively reverses cancer stemness and inhibits epithelial-mesenchymal transition, crucial mechanisms in cancer progression and resistance.
  • Preclinical data are strongest for pancreatic and colorectal cancers, with emerging evidence in gastric and preliminary findings in esophageal cancers.

Conclusions:

  • Betulinic acid is a promising natural compound with multi-targeted anticancer effects relevant to GI malignancies.
  • Nano-delivery systems offer a solution to BA's bioavailability issues, but formulation, scale-up, safety, and regulatory hurdles remain.
  • Addressing translational gaps in formulation is key to optimizing BA's clinical application and achieving progress in treating GI cancers.
Keywords:
betulinic acidcancer chemopreventiongastrointestinal cancersnano‐deliveryterpenoids

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