Lac color inhibits development of rat thyroid carcinomas through targeting activation of plasma hyaluronan-binding protein

Abstract

Coccid-derived natural food colorants contain active ingredients that potentiate inhibition of tissue proteolysis mediated by activation of plasma hyaluronan-binding protein (PHBP). In the present study, we examined the effect of lac color (LC) and cochineal extract (CE), representative coccid-derived colorants containing laccaic acid and carminic acid as active ingredients, in an intracapsular invasion model of experimental thyroid cancers using rats. One week after initiation with N-bis(hydroxypropyl)nitrosamine, male F344/NSIc rats were fed a powdered diet containing 5.0% LC or 3.0% CE during promotion with 0.15% sulfadimethoxine (SDM) in the drinking water for 13 weeks. Capsular invasive carcinomas (CICs) and lung metastases were decreased by LC treatment and accompanied by transcript downregulation on angiogenesis and PHBP-related tissue proteolysis in CICs. In contrast, CE upregulated angiogenesis-related genes in CICs. PHBP was expressed in capsular macrophages and thyroid proliferative lesions with increased intensity in CICs, and LC decreased PHBP-expressing CICs. The size of CICs and their proliferation activity, however, were unchanged compared with those treated with SDM alone. Suppression of cancer by invasion by LC was more evident after an eight-week treatment, exhibiting a profound decrease in tenascin-C-positive early invasive foci and marked reductions in capsular inflammation and fibrosis. These results suggest that LC and CE exerted dissimilar effects on CIC development, the former suppressing the initial step of neoplastic cell invasion into the capsule by targeting PHBP activity of macrophages and neoplastic cells on tissue proteolysis involving inflammatory responses and angiogenesis, and the latter promoting angiogenesis of developed CICs at later stages.

Lac water extract inhibits IFN-γ signaling through JAK2-STAT1-IRF1 axis in human melanoma

“… 12–14 Moreover, IFN-γ and chronic inflammation are also known to be involved in promoting tumor development. 34–36 In accordance with that evidence, it was also reported that the feeding of Lac color inhibits the development of thyroid carcinoma induced by sulfadimethoxine (SDM) in rats, 37 and that laccaic acid suppresses the SDM-induced T-cell-mediated inflammatory response. 38 Collectively, Lac might prevent inflammation-induced tumor development through its inhibitory activity in IFN-γ signaling.…”

Hyaluronic Acid Interacting Molecules Mediated Crosstalk between Cancer Cells and Microenvironment from Primary Tumour to Distant Metastasis

“…HMW-HA in healthy tissues inhibits PHBP expression, while its proteolytic activity is activated by HA fragments under the inflammatory condition [70]. Its activation may be associated with ECM remodelling, leading to a promotion of cell invasion, and has been reported to correlate with a malignant phenotype [157].…”

Fluctuations in cell proliferation, apoptosis, and cell cycle regulation at the early stage of tumor promotion in rat two-stage carcinogenesis models

“…One week later, animals were given drinking water with (DHPN + SDM) or without (DHPN-alone) SDM at 1,500 ppm for 4 weeks. The selected dose of SDM has shown to promote induction of follicular cell carcinomas after 13-week administration in a two-stage model (Kemmochi et al, 2012). To study the urinary bladder as the target organ, all animals were initiated with BBN at 500 ppm in the drinking water for 4 weeks.…”