Gene Expression Changes by Diallyl Trisulfide Administration in Chemically-induced Mammary Tumors in Rats

Abstract

Diallyl trisulfide (DATS) was shown to be a potent inhibitor of luminal-type MCF-7 xenograft growth in vivo. The present study was conducted to determine the preventive effect of DATS administration using an N -methyl- N -nitrosourea (MNU)-induced rat mammary tumor model, which shares molecular resemblance to luminal-type human breast cancers. The DATS administration (50 mg/kg body weight, 5 times/week) was safe, but did not reduce mammary tumor latency, incidence, burden or multiplicity. Therefore, we conducted RNA-seq analysis using mammary tumors from control and DATS-treated rats (n = 3 for each group) to gain insights into lack of mammary tumor prevention by this phytochemical. The gene ontology and the Kyoto encyclopedia of genes and genomes pathway analyses of the RNA-seq data revealed upregulation of genes associated with ribosomes, translation, peptide biosynthetic/metabolic process, and oxidative phosphorylation but downregulation of genes associated with mitogen-activated protein kinases. A total of 33 genes associated with ribosomes were significantly upregulated by DATS treatment, including RPL11 and RPS14 . Western blotting confirmed upregulation of RPL11 and neurofascin protein expression in mammary tumors from DATS-treated rats when compared to controls. A statistically significant increase in protein level of c-Jun N -terminal kinase 2 was also observed in tumors from DATS-treated rats when compared to controls. On the other hand, expression of complex I subunits NDUFV1 or NDUFS1 was not affected by DATS treatment. These results offer potential explanations for ineffectiveness of DATS in the chemically-induced rat mammary tumor model. Inhibitors of the proteins upregulated by DATS may be needed to improve chemopreventive efficacy of this phytochemical.

Effects of Garlic on Breast Tumor Cells with a Triple Negative Phenotype: Peculiar Subtype-Dependent Down-Modulation of Akt Signaling

“…Despite its elongated morphology, T174 is the only examined PDX-derived cell line expressing E-cadherin, which increased after GE administration, according to the reported effects of GE derivatives on this epithelial marker in breast tumor cells [18,23]. In this cell line, in which β-catenin was not modified, GE was unable to reduce migration and/or invasiveness, supporting previous data suggesting that the antitumor effect of some garlic derivatives on TNBC cells is mediated by the β-catenin pathway [26,47].…”

“…Among the natural compounds used in the treatment of various pathologies, garlic and its derivatives have proven useful in the prevention of breast cancer, as well as in inducing apoptosis and/or in reducing the invasive potential of human breast tumor cells in vitro and of animal tumor models in vivo [22,[24][25][26]. This suggests that the possibility of using garlic derivatives as adjuvants in the treatment of breast tumors that do not present satisfactory therapeutic approaches is not far away.…”

“…Garlic OSCs have been identified as functional substances with potential benefits against invasive breast cancer, counteracting the growth, migration, and invasiveness of breast tumor cells [21]. Most studies have been performed on Luminal MCF-7 and on triple negative MDA-MB-231 cell lines, in which individual garlic derivatives have been found to modulate cell cycle-and/or apoptosis-related proteins, as well as invasion/metastasis signaling pathways [22][23][24][25][26]. We recently also revealed the anti-cancer properties of garlic in non-invasive breast tumor cells, and its protective role against their malignant progression induced by low oxygen availability [27,28].…”

Garlic‐derived compounds: Epigenetic modulators and their antitumor effects

“…After DATS administration, the expression of RPL11 and its mRNA transcription was significantly upregulated in breast cancer (Hahm & Singh, 2022). These studies suggest the potential of garlic-derived compounds as anticancer drugs.…”

“…After oral administration, the tumor volume was significantly reduced in mice with er‐positive MCF‐7 cell xenotransplantation. After DATS administration, the expression of RPL11 and its mRNA transcription was significantly upregulated in breast cancer (Hahm & Singh, 2022). These studies suggest the potential of garlic‐derived compounds as anticancer drugs.…”