the absence of detectable bands may indicate that agmatine does not strongly activate the apoptotic pathway at the protein level in this cell model or that the experimental conditions ( e. g., insufficient lysate loading or low basal expression of these apoptotic proteins ) were inadequate to yield a visible signal on the blot. to the best of our knowledge, the present study is the first to demonstrate the anti - proliferative, anti - migration, anti - invasive, and anti - apoptotic effects of agmatine in the caco - 2, a model widely used for its enterocyte - like differentiation properties. colon epithelial cells are exposed to numerous dietary compounds and metabolites that can affect cell physiology. among these, polyamines are found in plant - and animal - based foods and fermented food products. polyamines are also produced by luminal colon bacteria. it has been reported that agmatine reduces cell proliferation in the ht - 29 cell lineand that treating ht - 29 cells with agmatine at a concentration of 1 mm reduces cell proliferation and leads to complete inhibition at a dose concentration of 5 mm. in the literature, it has been shown that agmatine affects adc - dependent cell apoptosis in the crc cell line ( hct116 ). agmatine produces a concentration - dependent inhibition of proliferation in six colorectal cancer cell lines, while colon carcinoma tissue samples displayed significantly lower agmatine levels compared to normal tissue. furthermore, agmatine demonstrated antiproliferative effects in tumor cells derived from colonic, hepatic, and neuronal origins. plasma agmatine levels in prostate cancer patients have been found to be significantly lower compared to healthy individuals; agmatine inhibits proliferation in prostate cancer cells and has been proposed as a potential biomarker and therapeutic agent. in another study, agmatine produced a dose - dependent antiproliferative effect in mcf - 7 breast cancer cells and sk - mg - 1 glioma cells, while also suppressing polyamine uptake. our results demonstrate that agmatine at concentrations of 6 mm, 7. 3 mm, and 9 mm significantly inhibits ros formation in caco - 2 cells at 72 h, suggesting that agmatine possesses the ability to alleviate oxidative stress and prevent ros - induced oxidative damage. agmatine has been shown to reduce ros production by activating the nrf2 / ho - 1 and pi3k / akt pathways in lps - induced bv - 2 microglia and raw 264. 7 macrophage cells, while increasing gpx activity and glutathione levels and inducing a “ pre - adaptive response ”. in a diabetes mellitus model, agmatine treatment has been demonstrated to elevate gpx and catalase levels in leukocytes and to reduce oxidative / nitrosative stress. additionally, agmatine has been reported to inhibit tumor cell proliferation by modulating polyamine metabolism in ht - 29 cells, with agmatine levels being significantly lower in colon cancer tissues compared to normal tissue, suggesting a potential association with polyamine dysregulation. another study by park et al. examined the protective effects of agmatine against cisplatin - induced cell death in an auditory cell line. the results indicated that agmatine inhibits apoptosis by suppressing bax and csp - 3 expression, though it does not directly decrease ros levels. these protective effects are thought to be associated with the regulatory role of agmatine on oxidative stress and inflammation. to the best of our knowledge, this is the first study to evaluate abc genes in agmatine treated caco - 2 cancer lines. a previous study has investigated the relationships between abcg2, abcc1, and abcb1 genes in two different colon cancer cell lines ( caco - 2 and ht - 29 ). in the ht - 29 cell line, a significant difference was found among the abcb1, abcg2, and abcc1 genes. it was shown that there was high up regulation of abcb1 and abcg2 but low upregulation of the abcc1 compared to the other genes. in the caco - 2 cell line, there was shown to be significant difference in all three genes; as a result, suggesting that the upregulation of expression of abc genes is directly related to cancer cell line. abcb1, abcc1, and abcc2 mrna levels were compared between caco - 2 cells and other colorectal cancer cell lines ( hct - 15, lovo, dld - 1, hct - 116, sw620 ). the results showed that abcb1 and abcc2 expression were higher in caco - 2 cells, whereas no significant differences were observed in ht - 29 - like cell lines. in another study that included the caco - 2 and ht - 29 cell lines, the promoter methylation levels of abcb1, abcc1, and abcg2 were investigated. the abcc1 promoter exhibited low methylation in both cell lines, while differences were observed in the methylation patterns of abcb1 and abcg2. according to our current results, no significant difference was found in the caco - 2 cell line that was treated with agmatine. our findings indicate that the major abc transporters abcg2, abcc1, and abcb1 are not modulated by agmatine treatment in colon cancer cells and do not mediate resistance to agmatine in caco - 2 tumor cells. according to the mrna expression levels of abcb1, abcc1, and abcg2 transporters in colorectal cancer patients, there is a significant difference in the expression levels of these abc transporters. the expression levels were found to be significantly higher in cancer patients. these findings showed that the expression of abc transporters is a potential biomarker for the diag nosis of crc patients. this study included no vehicle control or known cytotoxic positive control agents, such as cisplatin or doxorubicin. in this context, the absence of a positive cytotoxic control limits the direct comparison of our findings with the standard chemotherap eutic agents currently used in clinical practice. however, the primary objective of this study was to investigate the intrinsic biological effects of agmatine on crc cells. in this study, the inclusion of only the caco - 2 cell line among crc cell lines. on the other hand, the inclusion of only the caco - 2 cell line, without testing other colon cancer cell lines, represents one of the limitations of this current work. the caco - 2 cell line was selected because it is a widely used and well - characterized in vitro model in crc research, and it is particularly suitable for investigating cellular processes such as proliferation, migration, and invasion. however, the inclusion of additional colorectal cancer cell lines with distinc t genetic and molecular characteristics would have enhanced the translational relevance of the findings. one other limitation of the present study is that western blotting failed to detect bands corresponding to bax, bcl - 2, and csp - 3 in agmatine - treated caco - 2 cells, despite successfully visualizing of the internal control gapdh. consequently, changes in the expression of these proteins could not be confirmed at the protein level, limiting the validation of observations potentially made at the transcriptional or other levels. these findings highlight agmatine as a promising candidate for further investigation in colorectal cancer therapy, particularly through the modulation of proliferation, invasion, apoptosis, and oxidative stress pathways. the lack of effects on abc transporters further supports its potential as a selective and non - mdr - related agent. future studies including additional crc cell lines, in vivo models, and comparisons with established chemotherap eutic agents will be essential for fully elucidating its therapeutic potential and mechanisms of action. strategies to control hiv - 1 replication without antiviral therapy are needed to achieve a functional cure. to exploit the innate antiviral function of restriction factor cytidine deaminase apobec3g ( a3g ), we developed self - activating lentiviral vectors that efficiently deliver hiv - 1 vif - resistant mutant a3g - d128k to target cells.