The combination of thymoquinone and paclitaxel shows anti-tumor activity through the interplay with apoptosis network in triple-negative breast cancer.
Tumour Biol
; 37(4): 4467-77, 2016 Apr.
Article
de En
| MEDLINE
| ID: mdl-26500095
ABSTRACT
Thymoquinone (TQ) is the active ingredient of Nigella sativa which has a therapeutic potential in cancer therapy and prevention. In this study, TQ has been shown to induce specific cytotoxicity and apoptosis and to inhibit wound healing in triple-negative breast cancer cell line. TQ also inhibited cancer growth in a mouse tumor model. Moreover, TQ and paclitaxel (Pac) combination inhibited cancer growth in cell culture and in mice. Genes involved in TQ and TQ-Pac-mediated cytotoxicity were studied using focused real-time PCR arrays. After bioinformatic analysis, genes in apoptosis, cytokine, and p53 signaling categories were found to be modulated with a high significance in TQ-treated cells (p < 10(-28), p < 10(-8), and p < 10(-6), respectively). Important to note, TQ has been found to regulate the genes involved in the induction of apoptosis through death receptors (p = 5.5 × 10(-5)). Additionally, tumor suppressor genes such as p21, Brca1, and Hic1 were highly upregulated by TQ and TQ-Pac combination. Interestingly, when cells were treated with high dose TQ, several growth factors such as Vegf and Egf were upregulated and several pro-apoptotic factors such as caspases were downregulated possibly pointing out key pathways manipulated by cancer cells to resist against TQ. In cells treated with the combination of TQ and Pac, genes in apoptosis cascade (p < 10(-12)), p53 signaling (p = 10(-5)), and JAK-STAT signaling (p < 10(-3)) were differentially expressed. TQ has also been shown to induce protein levels of cleaved Caspase-3, Caspase-7, and Caspase-12 and PARP and to reduce phosphorylated p65 and Akt1. The in vivo therapeutic potential of TQ-Pac combination and the genetic network involved in this synergy have been shown for the first time to the best of our knowledge.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Carcinome d'Ehrlich
/
Protocoles de polychimiothérapie antinéoplasique
/
Apoptose
/
Tumeurs du sein triple-négatives
/
Tumeurs expérimentales de la mamelle
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
Tumour Biol
Sujet du journal:
NEOPLASIAS
Année:
2016
Type de document:
Article
Pays d'affiliation:
Turquie