Targeting Cancer Cells with Precision: The Therapeutic Potential of Curcumin-Albumin Conjugations
Abstract
Curcumin belongs to the family of ginge and is known to bear several anticancer activities. This advantage is followed by limitations like low bioavailability, stability, and solubility. Thus affecting its development as future cancer therapy. Albumin on the other hand, is known as an abundant protein present in plasma. Advantages of using albumin as a carrier are great biocompatibility, ability to bind to several drug types and improve in cytotoxic effect. The conjugation of curcumin and albumin has been researched and provides a great result on some cancer models. Findings of these studies prove the development of curcumin as a cancer therapy agent is limitless and could be made specific to cancer cells by benefiting from cancer cell characteristics for future development.
Keywords : curcumin, cancer, carrier, albumin
Introduction
Cancer has been ranked as one of the deadliest diseases in the world. Mortality numbers as high as 600 thousand have been reported in 2023 and have been followed with poor outcomes and high probability of recurrence. This matter is worsened by both late diagnosis and drug resistance. Multidrug resistance is also known to contribute to unresponsive therapy in up to 90% patients (de Andrade Carli et al., 2013). Current therapy like chemotherapy has found its limits as well. The unspecificity of chemotherapy has caused some discomforts to patients such as hair loss which affect patients emotionally. This became an urge to find an alternative to cancer therapy with modifications to ensure specificity. One of the sources of agents for cancer therapy to consider is coming from plants.
A plant known to have a pleasant taste and an unique yellow color have been researched for ages. Turmeric (Curcuma longa) is part of the ginger family and varsely distributed throughout the world with the highest cultivation in southeast Asian countries like Pakistan, Indonesia, and Cambodia. Its rhizomes have contributed the most to its health benefit because of curcumin presence. Curcumin alone can modulate cell cycle (Larasati et al., 2018) which is responsible for controlling cell proliferation. Other compounds bearing anticancer activity in turmeric are cinnamaldehyde and palmitic acid which known to enhance apoptosis (Liu et al., 2020), followed by beta-Curcumene and α-turmerone in inhibiting cancer growth (Nair et al., 2019; Sharma et al., 2022). Although curcumin has limits like poor bioavailability and solubility which restricts it to be developed further. This leads to the concern of finding an effective carrier for curcumin.
Carrier is, undoubtedly, an important component of a drug. Proper carrier leads to a satisfactory outcome. Low bioavailability has been the problem of several drugs and several approaches have also been done to overcome it. One of the approaches is applying a protein as a carrier by benefitting from cancer cell characteristics. Protein with high biocompatibility because of its abundant presence in blood is albumin (Singh et al., 2019). Albumin has the ability to bind to several overexpressed receptors such as gp60 and SPARC which enhances drug uptake and avoidance of drug efflux (Hassanin & Elzoghby, 2020). Another approach by encapsulating albumin and drug is also known to prolong half-life of drugs and increasing accumulation inside tumor cells (Hoogenboezem & Duvall, 2018). Therefore, albumin is a potential drug carrier to be implemented in vanishing limitance of curcumin as cancer therapy and helps with enhancing specificity to only cancer cells.
The researchers so far have focused on the potency of curcumin as a prospect to cancer therapy, yet, limitance like bioavailability becomes a problem to mend by collaborating it with albumin as a very potential optimum carrier. Thus, in this review, we explained more detail about the effect while discussing the result of conjugating it with albumin as a potential carrier to lower adverse effects by increasing specificity.
Discussion
a. Anticancer activities of curcumin
Previous studies explained several approaches of curcumin to possess anticancer activity. Study by Meiyanto et al (2014) explained the ability of curcumin to bind to proteins involved in proliferative signals. These overexpressed proteins when being bound could suppress cancer cell growth. When bound to IKK protein, curcumin suppressed the NF-kB pathway and showed the same effect when bound to ER as well. (Hoang Dang et al., 2024).
Entire studies mentioned above showed the prospect of curcumin mostly being an apoptotic inductor. This pathway is regarded as one of promising targets for controlling cancer growth and is an outstanding approach to be developed further.
b. Albuminated curcumin to resolve curcumin’s limitations
Albumin has several free functional residues which allows it to bind to a variety of drugs (Cho et al., 2022). Conjugating albumin aims to target one of cancer characteristics that relies highly on albumin supply for nutritional needs, thus improving selectivity of cancer treatment (Zeeshan et al., 2021). A study conducted by Aravind and Krishnan (2016) thoroughly showed that conjugation increases aqueous solubility. This affects the bioavailability as well since drugs better be dissolved in aqueous in order to be transported to targeted sites (Agrawal et al., 2016). Previous study also explained that albuminated curcumin is able to retain curcumin’s effects on cancer cells and even resulted in better cytotoxic effect compared to curcumin on MCF7 cells (Matloubi & Hassan, 2020). Other than enhancing solubility and cytotoxicity, the conjugation also exhibits better endurance to acidity compared to curcumin alone which shows a repair to stability problem of curcumin (Y.-J. Wang et al., 1997). Hence albumin is a possible approach to develop in order to make use of curcumin with higher solubility, stability, and cytotoxic activity which then could improve development of curcumin as a potential cancer therapy agent.
Conclusion
The general conclusion of this review article is that several constituents present in Curcuma longa have proven to be effective in diminishing cancer cells with curcumin being the abundant compound. Its prominent effects also accompanied with solubility, bioavailability, and stability limitation, thus toughening the future prospects of using it as an anticancer agent. Innovating albumin as a carrier to curcumin is proven to resolve several limitations of curcumin. All of these findings aim to be a starting point for future research in developing curcumin to be a new propelling anticancer agent.
References
Agrawal, A., Majumdar, A., & Jain, A. (2016). Self Emusifying Drug Delivery System for Improving Bioavailability.
Aravind, S. R., & Krishnan, L. K. (2016). Curcumin-albumin conjugates as an effective anti-cancer agent with immunomodulatory properties. International Immunopharmacology, 34, 78–85.
https://doi.org/10.1016/j.intimp.2016.02.010
Cho, H., Jeon, S. I., Ahn, C.-H., Shim, M. K., & Kim, K. (2022). Emerging albumin-binding anticancer drugs for tumor-targeted drug delivery: Current understandings and clinical translation. Pharmaceutics, 14(4), 728.
https://doi.org/10.3390/pharmaceutics14040728
Da’i, M., Suhendi, A., Meiyanto, E., Jenie, U. A., & Kawaichi, M. (2017). APOPTOSIS INDUCTION EFFECT OF CURCUMIN AND ITS ANALOGS PENTAGAMAVUNON-0 AND PENTAGAMAVUNON-1 ON CANCER CELL LINES. Asian Journal of Pharmaceutical and Clinical Research, 10(3), 373.
https://doi.org/10.22159/ajpcr.2017.v10i3.16311
de Andrade Carli, C. B., Quilles, M. B., & Carlos, I. Z. (2013). Chapter 16 - Natural Products with Activity against Multidrug-Resistant Tumor Cells (pp. 237–244). Academic Press.
Hassanin, I., & Elzoghby, A. (2020). Albumin-based nanoparticles: A promising strategy to overcome cancer drug resistance. Cancer Drug Resistance.
https://doi.org/10.20517/cdr.2020.68
Hoang Dang, P., Hoai Tran, T., Huu Le, T., Thi Nguyen, T., Binh Vong, L., Thanh Thi Nguyen, M., & Trung Nguyen, N. (2024). Design, synthesis, cytotoxic evaluation, and molecular docking of new alkyl triphenylphosphonium curcumin derivatives. ChemistrySelect, 9(10).
https://doi.org/10.1002/slct.202400176
Hoogenboezem, E. N., & Duvall, C. L. (2018). Harnessing albumin as a carrier for cancer therapies. Advanced Drug Delivery Reviews, 130, 73–89.
https://doi.org/10.1016/j.addr.2018.07.011
Larasati YA, Yoneda-Kato N, Nakamae I, Yokoyama T, Meiyanto E, Kato JY. Curcumin targets multiple enzymes involved in the ROS metabolic pathway to suppress tumor cell growth. Sci Rep. 2018; 8(1): 2039. doi: 10.1038/s41598-018-20179-6.
Liu, Y., An, T., Wan, D., Yu, B., Fan, Y., & Pei, X. (2020). Targets and mechanisms used by cinnamaldehyde, the main active ingredient in cinnamon, in the treatment of breast cancer. Frontiers in Pharmacology, 11.
https://doi.org/10.3389/fphar.2020.582719
Matloubi, Z., & Hassan, Z. (2020). HSA-curcumin nanoparticles: A promising substitution for Curcumin as a Cancer chemoprevention and therapy. DARU Journal of Pharmaceutical Sciences, 28(1), 209–219.
https://doi.org/10.1007/s40199-020-00331-2
Meiyanto, E., Putri, D. D. P., Susidarti, R. A., Murwanti, R., Sardjiman, S., Fitriasari, A., Husnaa, U., Purnomo, H., & Kawaichi, M. (2014). Curcumin and its Analogues (PGV-0 and PGV-1) Enhance Sensitivity of Resistant MCF-7 Cells to Doxorubicin through Inhibition of HER2 and NF-kB Activation. Asian Pacific Journal of Cancer Prevention, 15(1), 179–184.
https://doi.org/10.7314/apjcp.2014.15.1.179
Nair, A., Amalraj, A., Jacob, J., Kunnumakkara, A. B., & Gopi, S. (2019). Non-Curcuminoids from turmeric and their potential in cancer therapy and anticancer drug delivery formulations. Biomolecules, 9(1), 13.
https://doi.org/10.3390/biom9010013.
Ono, M., Higuchi, T., Takeshima, M., Chen, C., & Nakano, S. (2013). Antiproliferative and apoptosis-inducing activity of curcumin against human gallbladder adenocarcinoma cells. Anticancer research, 33(5), 1861–1866.
Shakibaei, M., Mobasheri, A., Lueders, C., Busch, F., Shayan, P., & Goel, A. (2013). Curcumin enhances the effect of chemotherapy against colorectal cancer cells by inhibition of nf-κb and src protein kinase signaling pathways. PLoS ONE, 8(2), e57218.
https://doi.org/10.1371/journal.pone.0057218
Sharma, M., Grewal, K., Jandrotia, R., Batish, D. R., Singh, H. P., & Kohli, R. K. (2022). Essential oils as anticancer agents: Potential role in malignancies, drug delivery mechanisms, and immune system enhancement. Biomedicine & Pharmacotherapy, 146, 112514.
https://doi.org/10.1016/j.biopha.2021.112514
Singh, B. G., Das, R. P., & Kunwar, A. (2019). Protein: A versatile biopolymer for the fabrication of smart materials for drug delivery. Journal of Chemical Sciences, 131(9), 1–14.
https://doi.org/10.1007/s12039-019-1671-0
Wang, Y.-J., Pan, M.-H., Cheng, A.-L., Lin, L.-I., Ho, Y.-S., Hsieh, C.-Y., & Lin, J.-K. (1997). Stability of curcumin in buffer solutions and characterization of its degradation products. Journal of Pharmaceutical and Biomedical Analysis, 15(12), 1867–1876.
https://doi.org/10.1016/s0731-7085(96)02024-9
Zeeshan, F., Madheswaran, T., Panneerselvam, J., Taliyan, R., & Kesharwani, P. (2021). Human serum albumin as multifunctional nanocarrier for cancer therapy. Journal of Pharmaceutical Sciences, 110(9), 3111–3117.
https://doi.org/10.1016/j.xphs.2021.05.001
Zhang, W., Bai, W., & Zhang, W. (2013). MiR-21 suppresses the anticancer activities of curcumin by targeting PTEN gene in human non-small cell lung cancer A549 cells. Clinical and Translational Oncology, 16(8), 708–713.
https://doi.org/10.1007/s12094-013-1135-9
