Guggulsterone Pharmacology in Cancer Therapeutics

Guggulsterone is a plant‐derived sterol extracted from the gum resin of Commiphora wightii. Over the past two decades, it has emerged as a multitargeted agent against malignant cells. Its principal anticancer mechanism involves induction of programmed cell death through the intrinsic, mitochondrial pathway, characterised by cytochrome c release and caspase activation. Concurrently, guggulsterone suppresses pro‐survival signalling cascades, notably NF-κB and PI3K/Akt, leading to downregulation of antiapoptotic proteins such as Bcl-2, survivin and inhibitor of apoptosis proteins. It also interferes with β-catenin and STAT3 pathways, exerts anti-angiogenic effects by reducing vascular endothelial growth factor, and can reverse P-glycoprotein-mediated multidrug resistance. Studies in diverse cancer cell lines have demonstrated its capacity to synergise with conventional chemotherapeutics, enhance tumour shrinkage in animal models and modulate inflammatory mediators. Pharmacokinetic investigations underscore potential drug–drug interactions via CYP3A4 inhibition, while formulation efforts aim to improve bioavailability and tissue targeting. The broad spectrum of guggulsterone’s actions, coupled with its relatively low toxicity profile, positions it as a promising lead for adjuvant therapy and further clinical translation in oncology.

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Guggulsterone Pharmacology in Cancer Therapeutics publication trend

The graph below shows the total number of articles in guggulsterone pharmacology in cancer therapeutics across all publications each year (not limited to Nature Index journals).

Technical terms

Phytosterol: A plant‐derived sterol structurally similar to cholesterol, often exhibiting bioactive properties.

Apoptosis: Programmed cell death involving caspase activation and DNA fragmentation.

Intrinsic mitochondrial pathway: Apoptotic route initiated by mitochondrial outer membrane permeabilisation and cytochrome c release.

NF-κB: A transcription factor that regulates genes involved in inflammation, cell survival and proliferation.

PI3K/Akt pathway: A signal transduction cascade promoting cell growth, survival and metabolism.

Farnesoid X receptor (FXR): A nuclear receptor that modulates bile acid homeostasis and can influence cancer cell proliferation.

References

1. Anti-cancer activity of guggulsterone by modulating apoptotic markers: a systematic review and meta-analysis. Frontiers in Pharmacology (2023).
2. Potential therapeutic targets of Guggulsterone in cancer. Nutrition & Metabolism (2017).
3. Pharmacology and Phytochemistry of Oleo‐Gum Resin of Commiphora wightii (Guggulu). Scientifica (2015).
4. Guggulsterone Inhibits NF-κB and IκBα Kinase Activation, Suppresses Expression of Anti-apoptotic Gene Products, and Enhances Apoptosis*. Journal of Biological Chemistry (2004).
5. Targeting beta-Catenin signaling to induce apoptosis in human breast cancer cells by z-Guggulsterone and Gugulipid extract of Ayurvedic medicine plant Commiphora mukul. BMC Complementary Medicine and Therapies (2013).
6. Z‐Guggulsterone Induces Apoptosis in Gastric Cancer Cells through the Intrinsic Mitochondria‐Dependent Pathway. The Scientific World JOURNAL (2021).
7. Z-Guggulsterone Is a Potential Lead Molecule of Dawa-ul-Kurkum against Hepatocellular Carcinoma. Molecules (2022).
8. Guggulsterone Targets Smokeless Tobacco Induced PI3K/Akt Pathway in Head and Neck Cancer Cells. PLOS ONE (2011).
9. CYP3A4 mediated pharmacokinetics drug interaction potential of Maha-Yogaraj Gugglu and E, Z guggulsterone. Scientific Reports (2021).