NIGERIAN JOURNAL OF CLINICAL PRACTICE, vol.1, no.27, pp.827-836, 2024 (SCI-Expanded)
Background: 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.
Methods: 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. Results: 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. Conclusion: 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.