Department of Basic Oncology, Institute of Oncology, Dokuz Eylul University, Izmir, Turkey.
Department of Animal Sciences, Institute of Health Sciences, Dokuz Eylul University, Izmir, Turkey.
Niger J Clin Pract. 2024 Jul 1;27(7):827-836. doi: 10.4103/njcp.njcp_512_23. Epub 2024 Jul 27.
Docetaxel (DOC) is the main chemotherapeutic agent for the treatment of advanced metastatic prostate cancer. Docetaxel shows anticancer effects by preventing the depolymerization of microtubules in the cell, therefore preventing cell division. However, the low survival effect of docetaxel has prompted researchers to search for novel therapeutic agents. Fucoidan (FUC) is a sulfated polysaccharide derived from brown algae. It has many bioactivities which makes fucoidan a promising anticancer agent. In this study, the potential anti-tumorigenic and preventive effects of fucoidan with or without docetaxel in prostate cancer were investigated by analyzing different cell death modalities.
The in-vivo six groups (n = 8) were conducted; preventive (Pt), docetaxel treated after preventive (Pt-D), control, fucoidan (FUC), docetaxel (DOC), and FUC and DOC (FUC+DOC) combination. Apoptotic, necroptotic, and autophagic cell death-related protein expressions were assessed in tumor tissues by using immunohistochemical staining. Oxidative stress-related lipid peroxidation, glutathione peroxidase, and glutathione levels were also determined in tumor tissues.
Although apoptotic, necroptotic, and autophagic cell deaths were significantly induced in agent-treated groups compared to the control. Apoptotic cell death was more significantly induced in FUC and FUC+DOC-treated groups. Necroptotic cell death was increased considerably by inducing MLKL protein expression in all treatment groups. In the FUC, Pt, and DOC groups, LC3A/B expressions were significantly increased. DOC, FUC+DOC, and Pt-D treatments caused a significant increase in Beclin-1 expression. Oxidative stress-related MDA, GPX, and GSH levels significantly decreased with FUC treatment. The anti-tumorigenic effects of FUC and DOC were also demonstrated through tumor size reduction.
According to the findings of this study, FUC inhibited tumor growth temporally and dimensionally, especially in preventive applications. FUC and FUC+DOC combinations in both treatment groups showed anti-tumorigenic effects. The results of this study suggest that fucoidan is a promising anticancer agent against prostate cancer. FUC can be considered as a preventive or treatment agent in prostate cancer therapy with DOC. Further studies are needed to fully elucidate the mechanism of action of fucoidan in metastatic prostate cancer.
多西紫杉醇（DOC）是治疗晚期转移性前列腺癌的主要化疗药物。多西紫杉醇通过阻止细胞内微管的解聚来发挥抗癌作用，从而阻止细胞分裂。然而，多西紫杉醇的低生存效果促使研究人员寻找新的治疗药物。褐藻糖胶（FUC）是一种源自褐藻的硫酸多糖。它具有许多生物活性，使褐藻糖胶成为一种很有前途的抗癌药物。在这项研究中，通过分析不同的细胞死亡方式，研究了褐藻糖胶与多西紫杉醇联合或不联合治疗前列腺癌的潜在抗肿瘤和预防作用。
进行了体内六组（n=8）实验；预防组（Pt）、预防后多西紫杉醇处理组（Pt-D）、对照组、褐藻糖胶组（FUC）、多西紫杉醇组（DOC）和褐藻糖胶和多西紫杉醇联合组（FUC+DOC）。采用免疫组织化学染色法检测肿瘤组织中与细胞凋亡、坏死性凋亡和自噬相关的蛋白表达。还测定了肿瘤组织中的氧化应激相关脂质过氧化、谷胱甘肽过氧化物酶和谷胱甘肽水平。
与对照组相比，各药物处理组的细胞凋亡、坏死性凋亡和自噬性细胞死亡均显著增加。FUC 和 FUC+DOC 处理组的细胞凋亡明显增加。所有治疗组均通过诱导 MLKL 蛋白表达增加坏死性凋亡细胞死亡。在 FUC、Pt 和 DOC 组中，LC3A/B 表达显著增加。DOC、FUC+DOC 和 Pt-D 处理导致 Beclin-1 表达显著增加。FUC 处理后，氧化应激相关 MDA、GPX 和 GSH 水平显著降低。FUC 和 DOC 的抗肿瘤作用也通过肿瘤体积的缩小得到证实。
根据本研究结果，褐藻糖胶在时间和空间上抑制肿瘤生长，尤其是在预防应用中。FUC 和 FUC+DOC 联合应用于两组治疗均显示出抗肿瘤作用。本研究结果表明褐藻糖胶是一种很有前途的前列腺癌治疗药物。褐藻糖胶可作为多西紫杉醇治疗前列腺癌的预防或治疗药物。需要进一步研究以充分阐明褐藻糖胶在转移性前列腺癌中的作用机制。
