Volume 9, Issue 3 (2023)                   Pharm Biomed Res 2023, 9(3): 169-172 | Back to browse issues page


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Law S K. Effectiveness of 5-aminolevulinic Acid Combined with Curcumin Mediating Photodynamic Therapy. Pharm Biomed Res 2023; 9 (3) :169-172
URL: http://pbr.mazums.ac.ir/article-1-528-en.html
Faculty of Science and Technology, The Technological and Higher Education Institute of Hong Kong, Tsing Yi, Hong Kong.
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Dear Editor
5-Aminolevulinic acid (5-ALA) is the mitochondria metabolite produced from glycine and succinyl-CoA, which is converted to protoporphyrin IX (PpIX) by the conjugation of eight itself molecules forming the “heme” group in the porphyrin ring (Figure 1) [1].



The PpIX is used as a photosensitizer (PS) with an absorption wavelength of 410 nm, and 5-ALA acts as a precursor or prodrug for PpIX in photodynamic therapy (PDT). Exogenous administration of excessive amounts of 5-ALA increases the production of PpIX during heme biosynthesis. It is eliminated after 24-48 h with a lower risk of long-term photosensitivity [2]. However, ALA/PDT has several disadvantages. For instance, the concentration of ALA is affected by its absorption and pharmacokinetics that do not fully cover the treatment area [3-5]. It also limits the depth of tumor penetration and causes pain [6].
Unsurprisingly, most plant extracts have no pharmaceutical activity on abnormal cells if they are not exposed to light. When the plant extracts are activated by light with a suitable wavelength, they act as a PS, which is strongly toxic to malignant cells [7]. Curcumin is a famous PS obtained from herbal plants, consisting of hydrophobic polyphenols found in the turmeric rhizome (Curcuma longa L.). It has various pharmaceutical properties, including anti-inflammatory, antioxidant, anti-bacterial, and antiviral properties [8, 9]. Curcumin has a broad absorption spectrum from 300 to 500 nm with a relatively high extinction coefficient [10]. Curcumin produces reactive oxygen species (ROS) and more specifically, singlet state oxygen (1O), hydrogen peroxide, and hydroxyl radicals [11]. ROS undergoes a destruction process in the PDT for treatment of cancers and diseases. A PS accumulates in the tumor tissue and illuminates it with light [12].
Curcumin-mediated PDT, combined with autophagy inhibitor, can further suppress epithelial-mesenchymal transition (EMT) in lung cancer cells. It may be a potential strategy against the invasion and migration of lung cancer.  Shao et al. investigated the apoptosis mechanism of curcumin-mediated PDT by detecting the levels of ROS, mitochondrial membrane potential, and related proteins [13]. Libby et al. examined the effect of curcumin-mediated PDT on oxidized low-density lipoprotein (ox-LDL)-treated vascular smooth muscle cells (VSMCs) to confirm whether these effects are mediated by autophagy. The therapy significantly promoted the autophagy level and inhibited the phenotypic transformation induced by ox-LDL [14]. Paolillo et al. examined the effect of combined curcumin-mediated PDT and artificial skin on Staphylococcus aureus infected wounds in rats. The PDT was performed with a curcumin gel and a blue LED light (450 nm, 80 mW/cm2) at the dose of 60 J/cm2 which accelerated the wound contraction [15].
Şueki et al. in a study in 2019 on the efficacy of 5-ALA-mediated PDT, used 10 μM of non-toxic doses of curcumin, which significantly reduced the PDT resistance in Caco-2 cells. They concluded that 5-ALA-mediated PDT, combined with curcumin, synergistically improves the antitumor efficacy of PDT on Caco-2, which is considered a highly resistive cancer cell line [16]. Tumor cell lines from adult T cell leukemia or lymphoma (ATL) are susceptible to specific cell death by visible light exposure after a short-term culture with 5-aminolevulinic acid, indicating that 5-ALA mediates the efficiency of PDT [17]. It is much better to use the PDT with other conventional therapies such as curcumin. Evidence showed that curcumin combined with PDT can overcome the limitation of curcumin’s low bioavailability, which is used to enhance the reactivity of curcumin and the efficacy of PDT [18].
The above mentioned materials demonstrates that 5-ALA-mediated PDT combined with curcumin may have some positive outcomes, such as enhancing the bioavailability and efficacy of PDT. However, more studies are needed to further investigate the effective concentrations (dosages) of the 5-ALA and curcumin in the human body. Hypocrellin-b and pyropheophorbide-a are other PS from herbal plants whose effects need to be studied.

Ethical Considerations

Compliance with ethical guidelines

There were no ethical considerations to be considered in this research.

Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors. 

Conflict of interest
The author declared no conflict of interest.



References
  1. Wachowska M, Muchowicz A, Firczuk M, Gabrysiak M, Winiarska M, Wańczyk M, et al. Aminolevulinic Acid (ALA) as a prodrug in photodynamic therapy of cancer. Molecules. 2011; 16(5):4140-64. [DOI:10.3390/molecules16054140] [PMCID]
  2. Park J, Lee YK, Park IK, Hwang SR. Current limitations and recent progress in nanomedicine for clinically available photodynamic therapy. Biomedicines. 2021; 9(1):85. [DOI:10.3390/biomedicines9010085] [PMID] [PMCID]
  3. Peng Q, Warloe T, Berg K, Moan J, Kongshaug M, Giercksky KE, et al. 5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges. Cancer 1997; 79(12):2282-308. [DOI:10.1002/(SICI)1097-0142(19970615)79:123.0.CO;2-O]
  4. O'Connor AE, Gallagher WM, Byrne AT. Porphyrin and nonporphyrin photosensitizers in oncology: Preclinical and clinical advances in photodynamic therapy. Photochem Photobiol. 2009; 85(5):1053-74. [DOI:10.1111/j.1751-1097.2009.00585.x] [PMID]
  5. Profio AE, Doiron DR. Dosimetry considerations in phototherapy. Med Phys. 1981; 8(2):190-6. [DOI:10.1118/1.594932] [PMID]
  6. Warren CB, Karai LJ, Vidimos A, Maytin EV. Pain associated with aminolevulinic acid-photodynamic therapy of skin disease. J Am Acad Dermatol. 2009; 61(6):1033-43. [DOI:10.1016/j.jaad.2009.03.048] [PMID] [PMCID]
  7. Kubrak TP, Kołodziej P, Sawicki J, Mazur A, Koziorowska K, Aebisher D. Some natural photosensitizers and their medicinal properties for use in photodynamic therapy. Molecules 2022; 27(4):1192. [DOI:10.3390/molecules27041192] [PMID] [PMCID]
  8. Salem M, Rohani S, Gillies ER. Curcumin, a promising anti-cancer therapeutic: A review of its chemical properties, bioactivity and approaches to cancer cell delivery. RSC Adv. 2014; 4:10815-29. [DOI:10.1039/c3ra46396f]
  9. Kunnumakkara AB, Bordoloi D, Harsha C, Banik K, Gupta SC, Aggarwal BB. Curcumin mediates anticancer effects by modulating multiple cell signaling pathways. Clin Sci (Lond). 2017; 131(15):1781-99. [DOI:10.1042/CS20160935] [PMID]
  10. Sreedhar A, Sarkar I, Rajan P, Pai J, Malagi S, Kamath V, et al. Comparative evaluation of the efficacy of curcumin gel with and without photo activation as an adjunct to scaling and root planing in the treatment of chronic periodontitis: A split mouth clinical and microbiological study. J Nat Sci Biol Med. 2015; 6(Suppl 1):S102-9. [DOI:10.4103/0976-9668.166100] [PMID] [PMCID]
  11. Chignell CF, Bilski P, Reszka KJ, Motten AG, Sik RH, Dahl TA. Spectral and photochemical properties of curcumin. Photochem Photobiol. 1994; 59(3):295-302.[DOI:10.1111/j.1751-1097.1994.tb05037.x] [PMID]
  12. Foresto E, Gilardi P, Ibarra LE, Cogno IS. Light-activated green drugs: How we can use them in photodynamic therapy and mass-produce them with biotechnological tools. Phytomedicine Plus. 2021; 1(3):100044. [DOI:10.1016/j.phyplu.2021.100044]
  13. Shao L, Zhu Y, Liao B, Wang G, Huang L, Yu L, et al. Effects of Curcumin-mediated photodynamic therapy on autophagy and epithelial-mesenchymal transition of lung cancer cells. Photodiagnosis Photodyn Ther. 2022; 38:102849. [DOI:10.1016/j.pdpdt.2022.102849] [PMID]
  14. Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011; 473(7347):317-25. [DOI:10.1038/nature10146] [PMID]
  15. Paolillo FR, Rodrigues PGS, Bagnato VS, Alves F, Pires L, Corazza AV. The effect of combined curcumin-mediated photodynamic therapy and artificial skin on Staphylococcus aureus-infected wounds in rats. Lasers Med Sci. 2021; 36(6):1219-26. [DOI:10.1007/s10103-020-03160-6] [PMID]
  16. Şueki F, Ruhi MK, Gülsoy M. The effect of curcumin in antitumor photodynamic therapy: In vitro experiments with Caco-2 and PC-3 cancer lines. Photodiagnosis Photodyn Ther. 2019; 27:95-9. [DOI:10.1016/j.pdpdt.2019.05.012] [PMID]
  17. Sando Y, Matsuoka KI, Sumii Y, Kondo T, Ikegawa S, Sugiura H, et al. Author correction: 5-aminolevulinic acid-mediated photodynamic therapy can target aggressive adult T cell leukemia/lymphoma resistant to conventional chemotherapy. Sci Rep. 2021; 11(1):6420. [DOI:10.1038/s41598-021-86066-9] [PMID] [PMCID]
  18. Xie L, Ji X, Zhang Q, Wei Y. Curcumin combined with photodynamic therapy, promising therapies for the treatment of cancer. Biomed Pharmacother. 2022; 146:112567. [DOI:10.1016/j.biopha.2021.112567] [PMID]
Type of Study: Letter to Editor | Subject: Natural products

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