β-Ionone for Cancer Therapy: Molecular Mechanisms, Apoptotic Signaling, Preclinical Evidence, and Translational Perspectives
8 affiliations
- 1Department of Environmental Science, Graphic Era (Deemed to Be University), Dehradun, Uttarakhand 248002, India
- 2Department of Bio-Sciences &Technology, Maharishi Markandeshwar (Deemed to Be University), Mullana-Ambala, Haryana 133207, India
- 3University Center for Research & Development (UCRD), Chandigarh University, Gharuan, Mohali, Punjab140413, India
- 4Department of Physics, MM Engineering College, Maharishi Markandeshwar (Deemed to Be University), Mullana, Ambala, Haryana 133207, India
- 5Centre for Research Impact and Outcome, Chitkara University, Rajpura, Punjab 140417, India
- 6Division of Research and Development, Lovely Professional University, Phagwara, Punjab 144411, India
- 7Centre of Excellence in Computational Research and Drug Discovery, Department of Bio-Sciences and Technology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to Be University), Mullana, Ambala 133207, India
- 8Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia
Abstract
β-Ionone is a naturally occurring C13-norisoprenoid apocarotenoid which is mainly derived from carotenoid cleavage and has gained significant attention due to its potential anticancer activity. Experimental investigations have shown that β-ionone has the ability to arrest the proliferation of cancer cells and to induce programmed cell death by several mechanisms depending on the type of tumors and experimental conditions. Mitochondrial apoptosis, such as Bax/Bcl-2 balance, cytochrome c release, activation of caspases, and p53-associated signaling, is the most consistently supported evidence for β-Ionone. Other mechanisms include modulation of the PI3K/Akt and MAPK/ERK signaling pathways, regulation of cell-cycle progression, generation of oxidative stress, and increased sensitivity to death-receptor-mediated apoptosis. Moreover, recent experimental studies have provided further support for the role of β-ionone in ferroptosis, as it was found to modulate the ferroptosis-associated proteins and Wnt/β-catenin signaling in gastric cancer models. By contrast, other mechanisms such as autophagy and the JAK/STAT3 signaling pathway are proposed mechanisms that need to be directly tested. Most importantly, evidence collected using β-ionone derivatives (such as esters and endoperoxides) differs from that collected from the parent. While promising preclinical results have been observed, translation is hampered by the lack of human pharmacokinetic data, uncertainties in bioavailability, and a lack of toxicity data and clinical trials. Target validation, characterization of the PHPD profile, safety assessment, formulation optimization, and clinically relevant in vivo validation should thus be given special attention in future studies.
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BibTeX
@article{kumar2026βionone,
title = {{β-Ionone for Cancer Therapy: Molecular Mechanisms, Apoptotic Signaling, Preclinical Evidence, and Translational Perspectives}},
author = {Ajay Kumar and Pooja Sharma and Soniya Goyal and Shallu Saini and Damandeep Kaur and Gurpreet Kaur Bhatia and Sandeep Sharma and Hardeep Singh Tuli and Hajed Obaid Alharbi and Arshad Husain Rahmani},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219521},
url = {https://www.mdpi.com/1422-0067/27/21/9521},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - β-Ionone for Cancer Therapy: Molecular Mechanisms, Apoptotic Signaling, Preclinical Evidence, and Translational Perspectives
AU - Ajay Kumar
AU - Pooja Sharma
AU - Soniya Goyal
AU - Shallu Saini
AU - Damandeep Kaur
AU - Gurpreet Kaur Bhatia
AU - Sandeep Sharma
AU - Hardeep Singh Tuli
AU - Hajed Obaid Alharbi
AU - Arshad Husain Rahmani
PY - 2026
DA - 2026/10/24
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219521
UR - https://www.mdpi.com/1422-0067/27/21/9521
AB - β-Ionone is a naturally occurring C13-norisoprenoid apocarotenoid which is mainly derived from carotenoid cleavage and has gained significant attention due to its potential anticancer activity. Experimental investigations have shown that β-ionone has the ability to arrest the proliferation of cancer cells and to induce programmed cell death by several mechanisms depending on the type of tumors and experimental conditions. Mitochondrial apoptosis, such as Bax/Bcl-2 balance, cytochrome c release, activation of caspases, and p53-associated signaling, is the most consistently supported evidence for β-Ionone. Other mechanisms include modulation of the PI3K/Akt and MAPK/ERK signaling pathways, regulation of cell-cycle progression, generation of oxidative stress, and increased sensitivity to death-receptor-mediated apoptosis. Moreover, recent experimental studies have provided further support for the role of β-ionone in ferroptosis, as it was found to modulate the ferroptosis-associated proteins and Wnt/β-catenin signaling in gastric cancer models. By contrast, other mechanisms such as autophagy and the JAK/STAT3 signaling pathway are proposed mechanisms that need to be directly tested. Most importantly, evidence collected using β-ionone derivatives (such as esters and endoperoxides) differs from that collected from the parent. While promising preclinical results have been observed, translation is hampered by the lack of human pharmacokinetic data, uncertainties in bioavailability, and a lack of toxicity data and clinical trials. Target validation, characterization of the PHPD profile, safety assessment, formulation optimization, and clinically relevant in vivo validation should thus be given special attention in future studies.
SN - 1422-0067
ER -