Triphlorethol‐A attenuates U251 human glioma cancer cell proliferation and ameliorates apoptosis through JAK2/STAT3 and p38 MAPK/ERK signaling pathways

Abstract

Glioma is the foremost recurrent type of brain tumor in humans; in particular, glioblastoma (GBM) is the main form of brain tumor (GBM) that is highly proliferative and impervious to apoptosis. Triphlorethol‐A (TA), a phlorotannin isolated from Ecklonia cava, exhibited cytoprotective, antioxidant, and anticancer properties. However, the exact molecular action of TA in the U251 human GBM cells remains unknown. This may be the first report on the antiproliferative and apoptotic mechanisms of TA on GBM. The cytotoxicity, intracellular reactive oxygen species (ROS), matrix metalloproteinase (MMP), and cell apoptosis activity of TA have been evaluated by the MTT assay and by DCFH‐DA, Rh‐123, AO/EB, and western blot analysis. The results obtained showed that TA abridged the viability of U251 cells, while MMP increased apoptosis by increasing the ROS levels in a time‐dependent manner. The results showed that a reduction in U251 cell proliferation was associated with the regulation of JAK2/STAT3 and p38 MAPK/ERK signaling pathways. TA was found to suppress pJAK, pSTAT3, p38 MAPK, and pERK phosphorylation, thereby causing Bax/Bcl‐2 imbalance, activating the caspase cascade and cytochrome c, and inducing apoptosis. Our findings showed that the suppression of JAK2/STAT3 and p38 MAPK/ERK signaling by TA results in cell growth arrest and stimulation of apoptosis in GBM cells. These studies justify the protective remedy of TA against GBM.

The Ocean’s Pharmacy: Health Discoveries in Marine Algae

“…Interestingly, anti-cancer activity featured the highest amount of microalgal studies (n = 7) compared to all the other bioactivities described in this review, which confirms it being a research hotspot [199]. In general, the tested macroalgal and microalgal extracts/compounds were successful in targeting one or multiple hallmarks of cancer-by displaying anti-proliferative effects (mainly through the induction of apoptosis) [72,[200][201][202][203][204][205][206][207][208][209][210][211][212][213][214], decreasing the inflammatory state [200,[211][212][213], migration capacity [215], angiogenesis potential [213], and adhesion properties [213]. When modulating oxidative stress, mechanisms to decrease cancerous cell survival differed between extracts or isolated compounds.…”

“…The methanol extract of Skeletonema marinoi [205] led to a decrease in NOx-generated ROS, increased antioxidant enzyme production, and decreased DNA damage in leukemia cells. On the other hand, the purified compounds triphlorethol-A [200] and fucoidan [210] increased oxidative stress by reducing antioxidant enzyme production, downregulating antioxidant pathways, and increasing DNA damage in brain glioma and oral cancer cells, respectively. However, both strategies were successful in decreasing cancer cell proliferation and survival, adding to the debate of therapeutic approaches towards ROS.…”

Design, synthesis and biological evaluation of a novel colchicine-magnolol hybrid for inhibiting the growth of Lewis lung carcinoma in Vitro and in Vivo

“…There is extensive evidence that the phosphorylation of mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase (ERK) subtype in particular, is closely associated with the growth and proliferation of tumor cells in cellular and animal experimental paradigms ( Yang et al, 2022 ; Yu et al, 2022 ). Specifically, the increase of phospho-ERK level was usually observed in cancer cell lines such as LLC cells, particularly those treated with pro-tumorogenic compounds ( Stoyanov et al, 2012 ), bio-molecules that could down-regulate ERK phosphorylation may thereby offer effective anti-tumor efficacy ( Shi et al, 2022 ; Yuan et al, 2022 ).…”

Roles of TRPM channels in glioma

“…For example, one study found that MAPK signaling is involved in TRPM8-mediated apoptosis of GBM cells, 162 and another study confirmed that inhibition of the MAPK signaling pathway leads to growth arrest and stimulates apoptosis of GBM cells. 163 Furthermore, TRPM8 interferes with cell cycle control via Cdc2, CaMKII, and cdc25C. 144 More specifically, TRPM8-mediated Ca2+ entry increases CaMKII activity by activating the BK channels and then inhibits the Cdc2 subunit of the mitotic promoter by inhibiting Cdc25C phosphatase phosphorylation.…”