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Anti-proliferative, Pro-apoptotic, and Chemosensitizing Potential of 3-Acetyl-11-keto-β-boswellic Acid (AKBA) Against Prostate Cancer Cells

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Abstract

Prostate cancer incidences are rising worldwide at an alarming rate. Drug resistance and relapse are two major challenges in the treatment of prostate cancer. Therefore, new multimodal, safe, and effective therapeutic agents are urgently required which could effectively mitigate the menace of tumor recurrence and chemo-resistance. Plant-derived products are increasingly being utilized due to their antioxidant, antibacterial, and anti-tumor potential. In the current study, 3-acetyl-11-keto-β-boswellic acid, a triterpenoid isolated from plant Boswellia, was utilized to ascertain its chemotherapeutic potential against human prostate cancer cells. Various in vitro assays including cell viability, nuclear staining, mitochondria potential, reactive oxygen species (ROS) generation, and quantification of apoptosis, were performed for the evaluation of the cytotoxic potential of AKBA. We observed that AKBA (10–50 µM) dose-dependently suppressed cell proliferation and caused programmed cell death in PC3 cells via both intrinsic and extrinsic pathway. Intriguingly, AKBA was also found to chemosensitize PC3 cells in synergistic combination with doxorubicin. To the best of our knowledge, this is the first study to document the synergistic chemosensitizing impact of AKBA when combined with doxorubicin in prostate cancer cells.This showcases the potential of AKBA in combinatorial therapy or adjuvant therapy for the management of prostate cancer. In sum, our results suggested that AKBA is a promising drug-like molecule against prostate cancer. Our investigation introduces a novel perspective, elucidating a previously unexplored dimension, and uncovering a compelling chemosensitizing phenomenon along with a strong synergistic effect arising from the concurrent application of these two agents.

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Data Availability

All datasets generated for this study are included in the article. Further inquiries can be directed to the corresponding author.

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Acknowledgements

The authors express their gratitude to DST-FIST for providing the necessary resources to carry out this research at Integral University. This manuscript has been assigned the communication number IU/R&D/2023-MCN0002087 by Integral University. Verma M also acknowledges the DST-INSPIRE Fellowship from the Department of Sciences and Technology, Government of India, for awarding the fellowship (SRF) for the smooth conduction of this work (DST-INSPIRE fellowship-IF180991). The Authors also acknowledge DST-FIST funding (SR/FST/LS-1/2017/13(C) to the Department of Biosciences, Integral University

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  1. Department of Biosciences, Integral Centre of Excellence for Interdisciplinary Research (ICEIR), Integral University, Lucknow, India

    Mahima Verma & Shireen Fatima

  2. Department of Biology, College of Science, University of Hail, Hail, Saudi Arabia

    Mohd Saeed

  3. Department of Biosciences, Integral University, Lucknow, India

    Irfan Ahmad Ansari

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  1. Mahima Verma
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MV performed all the experiments and wrote the manuscript. SF helped in data summarization. IAA conceptualized, edited, analyzed, and finalized the manuscript.

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Verma, M., Fatima, S., Saeed, M. et al. Anti-proliferative, Pro-apoptotic, and Chemosensitizing Potential of 3-Acetyl-11-keto-β-boswellic Acid (AKBA) Against Prostate Cancer Cells. Mol Biotechnol (2024). https://doi.org/10.1007/s12033-024-01089-7

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