(S)-3-(3,4-Dihydroxybenzyl) piperazine-2,5-dione (cyclo-Gly-L-DOPA or CG-Nio-CGLD) peptide loaded in Chitosan Glutamate-Coated Niosomes as anti-Colorectal cancer activity

Piri-Gharaghie et al. BMC Pharmacology and Toxicology https://doi.org/10.1186/s40360-024-00766-2 (2024) 25:44 BMC Pharmacology and Toxicology Open Access RESEARCH (S)-3-(3,4-Dihydroxybenzyl) piperazine-2,5dione (cyclo-Gly-L-DOPA or CG-Nio-CGLD) peptide loaded in Chitosan Glutamate-Coated Niosomes as anti-Colorectal cancer activity Tohid Piri-Gharaghie1*, Hedieh Ghourchian2, Golnoosh Rezaeizadeh3, Hamidreza Kabiri4,5, Negin Rajaei4,5, Aya Mohammed Dhiaa6, Ghazal Ghajari7 and Roghayeh Bahari8 Abstract Background Colorectal cancer (CRC), now the second most prevalent malignant tumor worldwide, is more prevalent in young adults. In recent decades, there has been progress in creating anti-colorectal cancer medications, including cytotoxic compounds. Objectives Novel anticancer drugs are needed to surmount existing obstacles. A recent study investigated the effectiveness of novel formulations in preventing colorectal cancer. Methods During this study, we assessed a new kind of niosome called cyclo-Gly-L-DOPA (CG-Nio-CGLD) made from chitosan glutamate. We evaluated the anti-colorectal cancer properties of CG-Nio-CGLD utilizing CCK-8, invasion assay, MTT assay, flow cytometry, and cell cycle analysis. The transcription of genes associated with apoptosis was analyzed using quantitative real-time PCR. At the same time, the cytotoxicity of nanomaterials on both cancer and normal cell lines was assessed using MTT assays. Novel anticancer drugs are needed to surmount existing obstacles. A recent study investigated the effectiveness of newly developed formulations in preventing colorectal cancer. Results The Nio-CGLD and CG-Nio-CGLD were spherical mean diameters of 169.12 ± 1.87 and 179.26 ± 2.17 nm, respectively. Entrapment efficiency (EE%) measurements of the Nio-CGLD and CG-Nio-CGLD were 63.12 ± 0.51 and 76.43 ± 0.34%, respectively. In the CG-Nio-CGLD group, the percentages of early, late, necrotic, and viable CL40 cells were 341.93%, 23.27%, 9.32%, and 25.48%. The transcription of the genes PP53, cas3, and cas8 was noticeably higher in the treatment group compared to the control group (P > 0.001). Additionally, the treatment group had lower BCL2 and survivin gene expression levels than the control group (P < 0.01). Additionally, CG-Nio-CGLD formulations demonstrated a biocompatible nanoscale delivery mechanism and displayed little cytotoxicity toward the CCD 841 CoN reference cell line. Conclusion These findings indicate that chitosan-based noisome encapsulation may enhance the effectiveness of CG-Nio-CGLD formulations in fighting cancer. Keywords Cyclo-Gly-L-DOPA, Niosome nanoparticles, Cytotoxicity, Antiapoptotic activity *Correspondence: Tohid Piri-Gharaghie Full list of author information is available at the end of the article © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Piri-Gharaghie et al. BMC Pharmacology and Toxicology (2024) 25:44 Introduction Cancer is a prevalent global source of morbidity and mortality. Cancer ranks as the second most common cause of death among noncommunicable diseases, following cardiovascular disease [1]. Colorectal cancer (CRC) is the third most common kind of cancer and contributes significantly to cancer-related deaths worldwide [2]. The prevalence of colorectal cancer in the rectum and distal colon is 22% and 28%, respectively, accounting for approximately 41% of all occurrences of colorectal malignancies [3]. Several lifestyle factors that can raise the chance of getting colorectal cancer include excessive alcohol use, a diet high in fat and low in fiber, smoking, lack of physical activity, ageing, and having a family history of the disease [4]. Several modalities have been employed in cancer management, such as immunotherapy, chemotherapy, surgical intervention, and radiation therapy. Regrettably, the toxicity of these treatments can have detrimental effects on both healthy and cancerous cells, resulting in side effects such as nausea, gastrointestinal issues, reduced white blood cell levels, and hair loss [5, 6]. Scientists are investigating new chemical compounds that could specifically target and destroy cancer cells while minimizing harm to healthy cells [7, 8]. Cancer chemoprevention involves the utilization of organic or synthetic substances derived from diet or other sources to impede or decelerate the progression of cancer [8]. Chemoprevention is becoming increasingly popular since it can effectively decrease the occurrence of cancer-related diseases while causing minimal severe side effects [9]. Piperazine-2,5-dione and similar treatments can efficiently preserve numerous bioactive compounds that have potential as potent anticancer drugs [10]. Glycine anhydride, or piperazine-2,5-dione, is a cyclic peptide where oxo groups replace the hydrogen atoms at positions 2 and 5. It is a member of the 2,5-diketopiperazine category and is classified as a cyclic peptide. Piperazine-2,5-dione, a natural compound, is the smallest cyclic peptide and serves as a helpful framework, exhibiting diverse structural modifications [11]. Piperazine-2,5-diones demonstrate superior resistance to enzymatic degradation compared to their linear counterparts [12]. They also possess frequent conformational rigidity and can interact with various biological targets [5]. As a result, they exhibit a wide range of biological impacts [13], such as antiviral [14], anticancer [15], antifouling agents [16], antioxidative [17], and anti-PAI-1 properties [18], among others. Piperazine-2,5-dione has become a sought-after and unique framework for exploring potent pharmacological medicines. A specific group of piperazine-2,5-diones, which includes XR334 [19], piperazine B [20], phenylahistin [21], and its chemical derivative plinabulin [15–21], have unchanged C-C double bonds at the 3- and 6-positions of the Piperazine-2,5-dione ring. Page 2 of 16 These chemicals demonstrate distinct and discernible variations in their ability to inhibit the (...truncated)