Carnosic Acid as a Promising Anticancer Agent: Mechanisms of Action and Therapeutic Potential Across Multiple Cancer Types
DOI:
https://doi.org/10.71193/jcid.20250001Keywords:
Anticancer, Breast cancer, Carnosic acid, Phenolic diterpene, Lung cancerAbstract
Carnosic acid (CA) is a phenolic diterpene that has multiple pharmacological actions that include neuroprotective, anti-inflammatory, antioxidant, and anticancer actions. However, its anticancer activity remains underexplored, and this study aims to fill that gap. The process involves browsing through Google Scholar, ScienceDirect, Web of Science, and PubMed. According to our study, CA has strong anticancer properties against a variety of cancers like breast, colon, colorectal, lung, liver, leukemia, cervical, ovarian, and prostate cancer. It induces apoptosis by reducing anti-apoptotic Bcl-2 expression and increasing pro-apoptotic Bax and Caspase-3 levels. CA reduces cell growth and migration by suppressing key signaling pathways like Akt/mTOR, PI3K, and MAPK, while also inhibiting the cell cycle. Numerous cancer types have shown these effects in both in vitro and in vivo investigations. The results indicate that CA is a viable cancer therapeutic option that merits more research into its clinical uses and pharmacokinetics.
Downloads
References
Aktar, A., Bhuia, S., Chowdhury, R., Ferdous, J., Khatun, M., Hasan, S. A., Mia, E., Hasan, R., & Islam, M. T. (2024). An Insight of Plant Source, Toxicological Profile, and Pharmacological Activities of Iridoid Loganic Acid: A ComprehensiveReview. Chemistry & biodiversity, 21(12), e202400874. https://doi.org/10.1002/cbdv.202400874 DOI: https://doi.org/10.1002/cbdv.202400874
Barni, M.V., Carlini, M.J., Cafferata, E.G., Puricelli, L., & Moreno, S. (2012). Carnosic acid inhibits the proliferation and migration capacity of human colorectal cancer cells. Oncology Reports, 27, 1041-1048. https://doi.org/10.3892/or.2012.1630 DOI: https://doi.org/10.3892/or.2012.1630
Bhat, A. A., Goyal, A., Thapa, R., Almalki, W. H., Kazmi, I., Alzarea, S. I., Singh, M., Rohilla, S., Saini, T. K., Kukreti, N., Meenakshi, D. U., Fuloria, N. K., Sekar, M., & Gupta, G. (2023). Uncovering the complex role of interferon-gamma in suppressing type 2 immunity to cancer. Cytokine, 171, 156376. https://doi.org/10.1016/j.cyto.2023.156376 DOI: https://doi.org/10.1016/j.cyto.2023.156376
Bhuia, M. S., Chowdhury, R., Afroz, M., Akbor, M. S., Al Hasan, M. S., Ferdous, J., Hasan, R., de Alencar, M. V. O. B., Mubarak, M. S., & Islam, M. T. (2025). Therapeutic Efficacy Studies on the Monoterpenoid Hinokitiol in the Treatment of Different Types of Cancer. Chemistry & biodiversity, e202401904. Advance online publication. https://doi.org/10.1002/cbdv.202401904 DOI: https://doi.org/10.1002/cbdv.202401904
Borhan, A., Bagherlou, A., & Ghayour, M. B. (2025). Evaluating the anticancer effects of carnosic acid against breast cancer: An In Vitro investigation. Tissue & cell, 93, 102718. Advance online publication. https://doi.org/10.1016/j.tice.2024.102718 DOI: https://doi.org/10.1016/j.tice.2024.102718
Cvetkovikj, I., Stefkov, G., Acevska, J., Stanoeva, J. P., Karapandzova, M., Stefova, M., Dimitrovska, A., & Kulevanova, S. (2013). Polyphenolic characterization and chromatographic methods for fast assessment of culinary Salvia species from South East Europe. Journal of chromatography. A, 1282, 38–45. https://doi.org/10.1016/j.chroma.2012.12.068 DOI: https://doi.org/10.1016/j.chroma.2012.12.068
Das, S., Joardar, S., Manna, P., Dua, T. K., Bhattacharjee, N., Khanra, R., Bhowmick, S., Kalita, J., Saha, A., Ray, S., De Feo, V., & Dewanjee, S. (2018). Carnosic Acid, a Natural Diterpene, Attenuates Arsenic-Induced Hepatotoxicity via Reducing Oxidative Stress, MAPK Activation, and Apoptotic Cell Death Pathway. Oxidative medicine and cellular longevity, 2018, 1421438. https://doi.org/10.1155/2018/1421438 DOI: https://doi.org/10.1155/2018/1421438
Debela, D. T., Muzazu, S. G., Heraro, K. D., Ndalama, M. T., Mesele, B. W., Haile, D. C., Kitui, S. K., & Manyazewal, T. (2021). New approaches and procedures for cancer treatment: Current perspectives. SAGE open medicine, 9, 20503121211034366. https://doi.org/10.1177/20503121211034366 DOI: https://doi.org/10.1177/20503121211034366
Duran, T., Koçak, N., & Karaselek, M. (2024). Carnosol and carnosic acid may be a promising anticancer agent in non-small cell lung cancer treatment. Cukurova Medical Journal, 49(1), 81-88. DOI: https://doi.org/10.17826/cumj.1399224
Einbond, L. S., Wu, H. A., Kashiwazaki, R., He, K., Roller, M., Su, T., Wang, X., & Goldsberry, S. (2012). Carnosic acid inhibits the growth of ER-negative human breast cancer cells and synergizes with curcumin. Fitoterapia, 83(7), 1160–1168. https://doi.org/10.1016/j.fitote.2012.07.006 DOI: https://doi.org/10.1016/j.fitote.2012.07.006
El-Huneidi, W., Bajbouj, K., Muhammad, J. S., Vinod, A., Shafarin, J., Khoder, G., Saleh, M. A., Taneera, J., & Abu-Gharbieh, E. (2021). Carnosic Acid Induces Apoptosis and Inhibits Akt/mTOR Signaling in Human Gastric Cancer Cell Lines. Pharmaceuticals, 14(3), 230. https://doi.org/10.3390/ph14030230 DOI: https://doi.org/10.3390/ph14030230
Foroughi-Gilvaee, M., Martirosyan, D., Mashayekhnia, M., Maadi, M., Sarvendani, M., & Maghsoumi, M. (2024). Exploring the potential of bioactive compounds in preventing cancer growth and progression: A comprehensive review. Bioactive Compounds in Health and Disease-Online ISSN: 2574-0334; Print ISSN: 2769-2426, 7(6), 302-324. DOI: https://doi.org/10.31989/bchd.v7i6.1370
Han, N. N., Zhou, Q., Huang, Q., & Liu, K. J. (2017). Carnosic acid cooperates with tamoxifen to induce apoptosis associated with Caspase-3 activation in breast cancer cells in vitro and in vivo. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 89, 827–837. https://doi.org/10.1016/j.biopha.2017.01.084 DOI: https://doi.org/10.1016/j.biopha.2017.01.084
Jiang, S., Qiu, Y., Wang, Z., Ji, Y., Zhang, X., Yan, X., & Zhan, Z. (2021). Carnosic Acid Induces Antiproliferation and Anti-Metastatic Property of Esophageal Cancer Cells via MAPK Signaling Pathways. Journal of oncology, 2021, 4451533. https://doi.org/10.1155/2021/4451533. DOI: https://doi.org/10.1155/2021/4451533
Liu, D., Wang, B., Zhu, Y., Yan, F., & Dong, W. (2018). Carnosic acid regulates cell proliferation and invasion in chronic myeloid leukemia cancer cells via suppressing microRNA-708. Journal of B.U.ON.: official journal of the Balkan Union of Oncology, 23(3), 741–746.
Maione, F., Cantone, V., Pace, S., Chini, M. G., Bisio, A., Romussi, G., Pieretti, S., Werz, O., Koeberle, A., Mascolo, N., & Bifulco, G. (2017). Anti-inflammatory and analgesic activity of carnosol and carnosic acid in vivo and in vitro and in silico analysis of their target interactions. British journal of pharmacology, 174(11), 1497–1508. https://doi.org/10.1111/bph.13545 DOI: https://doi.org/10.1111/bph.13545
Matsingou, T. C., Petrakis, N., Kapsokefalou, M., & Salifoglou, A. (2003). Antioxidant activity of organic extracts from aqueous infusions of sage. Journal of agricultural and food chemistry, 51(23), 6696–6701. https://doi.org/10.1021/jf034516o DOI: https://doi.org/10.1021/jf034516o
Mirza, F. J., Zahid, S., & Holsinger, R. M. D. (2023). Neuroprotective Effects of Carnosic Acid: Insight into Its Mechanisms of Action. Molecules (Basel, Switzerland), 28(5), 2306. https://doi.org/10.3390/molecules28052306 DOI: https://doi.org/10.3390/molecules28052306
Nadile, M., Sze, N. S. K., Fajardo, V. A., & Tsiani, E. (2024). Inhibition of Prostate Cancer Cell Survival and Proliferation by Carnosic Acid Is Associated with Inhibition of Akt and Activation of AMPK Signaling. Nutrients, 16(9), 1257. https://doi.org/10.3390/nu16091257. DOI: https://doi.org/10.3390/nu16091257
O’Neill, E. J., Sze, N. S. K., MacPherson, R. E. K., & Tsiani, E. (2024). Carnosic Acid against Lung Cancer: Induction of Autophagy and Activation of Sestrin-2/LKB1/AMPK Signalling. International Journal of Molecular Sciences, 25(4), 1950. https://doi.org/10.3390/ijms25041950. DOI: https://doi.org/10.3390/ijms25041950
Ossikbayeva, S., Khanin, M., Sharoni, Y., Trachtenberg, A., Tuleukhanov, S., Sensenig, R., Rom, S., Danilenko, M., & Orynbayeva, Z. (2021). Curcumin and Carnosic Acid Cooperate to Inhibit Proliferation and Alter Mitochondrial Function of Metastatic Prostate Cancer Cells. Antioxidants, 10(10), 1591. https://doi.org/10.3390/antiox10101591 DOI: https://doi.org/10.3390/antiox10101591
Park, S. Y., Song, H., Sung, M. K., Kang, Y. H., Lee, K. W., & Park, J. H. (2014). Carnosic acid inhibits the epithelial-mesenchymal transition in B16F10 melanoma cells: a possible mechanism for the inhibition of cell migration. International journal of molecular sciences, 15(7), 12698–12713. https://doi.org/10.3390/ijms150712698 DOI: https://doi.org/10.3390/ijms150712698
Parsa N. (2012). Environmental factors inducing human cancers. Iranian journal of public health, 41(11), 1–9.
Samarghandian, S., Azimi-Nezhad, M., & Farkhondeh, T. (2018). Anti-Carcinogenic Effects of Carnosol-An Updated Review. Current drug discovery technologies, 15(1), 32–40. https://doi.org/10.2174/1570163814666170413121732 DOI: https://doi.org/10.2174/1570163814666170413121732
Shin, H. B., Choi, M. S., Ryu, B., Lee, N. R., Kim, H. I., Choi, H. E., Chang, J., Lee, K. T., Jang, D. S., & Inn, K. S. (2013). Antiviral activity of carnosic acid against respiratory syncytial virus. Virology journal, 10, 303. https://doi.org/10.1186/1743-422X-10-303 DOI: https://doi.org/10.1186/1743-422X-10-303
Steiner, M., Priel, I., Giat, J., Levy, J., Sharoni, Y., & Danilenko, M. (2001). Carnosic acid inhibits proliferation and augments differentiation of human leukemic cells induced by 1,25-dihydroxyvitamin D3 and retinoic acid. Nutrition and cancer, 41(1-2), 135–144. https://doi.org/10.1080/01635581.2001.9680624 DOI: https://doi.org/10.1080/01635581.2001.9680624
Su, K., Wang, C. F., Zhang, Y., Cai, Y. J., Zhang, Y. Y., & Zhao, Q. (2016). The inhibitory effects of carnosic acid on cervical cancer cells growth by promoting apoptosis via ROS-regulated signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 82, 180–191. https://doi.org/10.1016/j.biopha.2016.04.056 DOI: https://doi.org/10.1016/j.biopha.2016.04.056
Wei, J., Liang, Q., Guo, Y., Zhang, W., & Wu, L. (2021). A Deep Insight in the Antioxidant Property of Carnosic Acid: From Computational Study to Experimental Analysis. Foods (Basel, Switzerland), 10(10), 2279. https://doi.org/10.3390/foods10102279 DOI: https://doi.org/10.3390/foods10102279
Wu, Q., Wang, X., Pham, K., Luna, A., Studzinski, G. P., & Liu, C. (2020). Enhancement of sorafenib-mediated death of Hepatocellular carcinoma cells by Carnosic acid and Vitamin D2 analog combination. The Journal of steroid biochemistry and molecular biology, 197, 105524. https://doi.org/10.1016/j.jsbmb.2019.105524 DOI: https://doi.org/10.1016/j.jsbmb.2019.105524
Yan, M., Li, G., Patiwala, S. M., Householter, E., & Johnson, J. J. (2014). Anti-cancer activity of rosemary extract in colon cancer cells: Involvement of Nrf2 and ERK pathways. Cancer Research, 74(19_Supplement), 4122-4122. DOI: https://doi.org/10.1158/1538-7445.AM2014-4122
Zappavigna, S., Cossu, A. M., Grimaldi, A., Bocchetti, M., Ferraro, G. A., Nicoletti, G. F., Filosa, R., & Caraglia, M. (2020). Anti-Inflammatory Drugs as Anticancer Agents. International journal of molecular sciences, 21(7), 2605. https://doi.org/10.3390/ijms21072605 DOI: https://doi.org/10.3390/ijms21072605
Downloads
Published
Data Availability Statement
Data will be made available on request.
Issue
Section
Categories
License
Copyright (c) 2025 Noshin Tasnim Yana Yana, Md. Nasimul Haque Shipon, Asmaul Husna Bristy, Fowjia Ahmed Safa, Md. Arif Hossain, Md Sakib Al Hasan (Author)

This work is licensed under a Creative Commons Attribution 4.0 International License.
