Docosahexaenoic acid inhibits 12-O-tetradecanoylphorbol-13- acetate-induced fascin-1-dependent breast cancer cell migration by suppressing the PKCδ- and Wnt-1/β-catenin-mediated pathways

Abstract

Fascin-1, an actin-bundling protein, plays an important role in cancer cell migration and invasion; however, the underlying mechanism remains unclear. On the basis of a 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced cell migration model, it was shown that TPA increased fascin-1 mRNA and protein expression and fascin-1-dependent cell migration. TPA dose- and time-dependently increased PKCδ and STAT3α activation and GSK3β phosphorylation; up-regulated Wnt-1, β-catenin, and STAT3α expression; and increased the nuclear translocation of β-catenin and STAT3α. Rottlerin, a PKCδ inhibitor, abrogated the increases in STAT3α activation and β-catenin and fascin-1 expression. WP1066, a STAT3 inhibitor, suppressed TPA-induced STAT3α DNA binding activity and β-catenin expression. Knockdown of β-catenin attenuated TPA-induced fascin-1 and STAT3α expression as well as cell migration. In addition to MCF-7, migration of Hs578T breast cancer cells was inhibited by silencing fascin-1, β-catenin, and STAT3α expression as well. TPA also induced Wnt-1 expression and secretion, and blocking Wnt-1 signaling abrogated β-catenin induction. DHA pretreatment attenuated TPA-induced cell migration, PKCδ and STAT3α activation, GSK3β phosphorylation, and Wnt-1, β-catenin, STAT3α, and fascin-1 expression. Our results demonstrated that TPA-induced migration is likely associated with the PKCδ and Wnt-1 pathways, which lead to STAT3α activation, GSK3β inactivation, and β-catenin increase and up-regulation of fascin-1 expression. Moreover, the anti-metastatic potential of DHA is partly attributed to its suppression of TPA-activated PKCδ and Wnt-1 signaling.

7‐Methoxy‐luteolin‐8‐C‐β‐6‐deoxy‐xylo‐pyranos‐3‐uloside exactly (mLU8C‐PU) isolated from Arthraxon hispidus inhibits migratory and invasive responses mediated via downregulation of MMP‐9 and IL‐8 expression in MCF‐7 breast cancer cells

“…The expression of MMP‐9 and IL‐8 is directed by cis‐acting transcription regulatory elements for AP‐1 and NF‐κB transcription factors. In addition, STAT3 acts as a key transcription factor in the regulation of migration in breast cancer cells . We already showed that mLU8C‐PU decreases TPA‐induced mRNA and protein levels of MMP‐9 and IL‐8.…”

The Anticancer Properties of Tanshinones and the Pharmacological Effects of Their Active Ingredients

“…Angiogenesis is a vital step in the physiological process of tissue repair and regeneration, bone remodeling and reproduction, and embryonic development (Folkman, 2006;Garona et al, 2018;Annese et al, 2019). Moreover, it also played a critical role in the progression of tumor formation, infiltration, invasion, and metastasis (Carmeliet, 2006;Seano et al, 2014;Lii et al, 2016;Ao et al, 2017;Yang et al, 2017). Thus, inhibition of angiogenesis has become an effective strategy for cancer therapy.…”

12-O-Tetradecanoylphorbol-13-acetate (TPA) is anti-tumorigenic in liver cancer cells via inhibiting YAP through AMOT

“…Commonly, TPA is employed as a tumor-promoting agent for skin carcinogenesis in rodents and is associated with increased cell proliferation in malignant cells from several types of tumors, such as melanoma and breast and oral cancer345. However, the function of TPA is controversial because a decrease in cell proliferation capacity has also been observed in TPA-treated lymphoma cells compared to controls67.…”