Fucoxanthin induces apoptosis in acute lymphoblastic leukaemia cell line by damaging the endoplasmic reticulum

PURPOSE : The purpose of this study was to examine the impact of fucoxanthin on acute lymphoblastic leukemia (ALL) cell line Nalm6 and the roles played by mitochondria and the endoplasmic reticulum in this process. METHODS : In vitro experiments were conducted using the acute lymphoblastic leukemia cell line Nalm6 to evaluate the cytotoxic effects of fucoxanthin and dexamethasone, both as individual agents and in combination. The mechanism of action of fucoxanthin on ALL cell lines was investigated using MTT assays, flow cytometry, Seahorse assays, western blot and transmission electron microscopy. RESULTS : Compared to the control group, fucoxanthin significantly suppressed the proliferation of Nalm6, triggered apoptosis by regulating the expression of apoptosis-related protein, and arrested the cell cycle at the G0/G1 phase in the in vitro experiments. When combined with the clinical drug dexamethasone, fucoxanthin exhibited synergistic effects in inducing apoptosis. Transcriptomics sequencing revealed that the oxidative phosphorylation and protein processing in endoplasmic reticulum pathway was notably affected. Following treatment with fucoxanthin, the mitochondrial membrane potential became abnormal, the mitochondrial ATP consumption rate decreased, and the mitochondrial ATP production rate were reduced. Mitochondrial damage, including the disappearance of mitochondrial cristae and matrix swelling, was observed via transmission electron microscopy, along with signs of endoplasmic reticulum stress. The Western blot results indicate that the GRP78-PERK-CHOP signalling axis is activated following treatment with fucoxanthin. The co-application of the calcium chelator BAPTA-AM with fucoxanthin mitigated the mitochondrial damage caused by fucoxanthin. CONCLUSION : Our findings suggest that fucoxanthin induces apoptosis by initiating endoplasmic reticulum stress, which subsequently leads to mitochondrial damage. Fucoxanthin holds potential for further investigation as a treatment for acute lymphoblastic leukemia.