Review
DOI DOI: 10.65239/botanicaldrugs.2026.06

Targeting Apoptotic Pathways in Cancer with Emodin: Intrinsic, Extrinsic, and Caspase-Independent Mechanisms

Gorky Guha1, Shreya Das1, Jhansi Kompala1, Sohith Reddy Korlagunta1, Sukant Khurana2, Alfredo Ghezzi3, Lakshminarayanan Karthik1, Abhijit G Banerjee4
  1. 1 IonCure Tech, New Delhi, India
  2. 2 Lyda Hill Institute for Human Resilience, University of Colorado, Colorado Springs, Colorado, USA
  3. 3 Department of Biology, University of Puerto Rico, USA
  4. 4 Genomic Bio-Medicine Research and Incubation, Chhattisgarh (CGBMRI), Durg-491001, India

Abstract

Programmed cell death, also known as apoptosis, is crucial for maintaining cellular homeostasis and plays a significant role in tumor development, progression, and resistance to treatment. Evading apoptosis has been a characteristic of cancer, and apoptotic signaling pathways have been proposed as targets of anticancer drug development. Emodin, a naturally occurring anthraquinone produced by medicinal plants, has become a promising anti-cancer agent, inducing apoptosis in a wide range of cancer types, including those resistant to chemo- and biotherapy, through both p53-dependent and p53-independent mechanisms. This review provides a summary of the existing knowledge on the cellular and molecular basis of emodin-induced apoptosis, especially its regulation of extrinsic death receptor signaling and intrinsic mitochondrial pathways. Emodin facilitates cytochrome c release, depolarization of the mitochondrial membrane, and caspase activation by regulating B-cell lymphoma 2 (Bcl-2) family proteins and death receptor-associated complexes. In addition, the increasing amount of evidence also indicates that emodin-mediated apoptosis is tightly connected with the formation of reactive oxygen species and endoplasmic reticulum-mediated stress, cross-talk with autophagic and cell cycle regulatory pathways. The preclinical evidence indicates that emodin is a potent tumor growth inhibitor, apoptotic resistance regulator, and cancer stem cell-related signaling modulator, and also an augmenter of the efficacy of conventional chemotherapeutic treatment. Clinical translation is, however, limited due to low bioavailability, metabolic rate, and pharmacokinetic impairments. Further studies should be conducted on formulation strategies, structural optimization, and rational combination therapies to maximize the apoptotic and anticancer properties of emodin.

How to Cite

1.
Guha G, Das S, Kompala J, Korlagunta SR, Khurana S, Ghezzi A, et al. Targeting Apoptotic Pathways in Cancer with Emodin: Intrinsic, Extrinsic, and Caspase-Independent Mechanisms. Botanical Drugs [Internet]. 2026 Jul. 5 [cited 2026 Jul. 12];1:77-92. Available from: https://botanicaldrugs.org/index.php/pub/article/view/19
Endnote/Zotero/Mendeley (RIS) BibTeX

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