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- Title
Thymoquinone as an anticancer agent: evidence from inhibition of cancer cells viability and invasion in vitro and tumor growth in vivo.
- Authors
Attoub, Samir; Sperandio, Olivier; Raza, Haider; Arafat, Kholoud; Al‐Salam, Suhail; Al Sultan, Mahmood Ahmed; Al Safi, Maha; Takahashi, Takashi; Adem, Abdu
- Abstract
Phytochemical compounds are emerging as a new generation of anticancer agents with limited toxicity in cancer patients. The purpose of this study was to investigate the potential impact of thymoquinone ( TQ), the major constituent of black seed, on survival, invasion of cancer cells in vitro, and tumor growth in vivo. Exposure of cells derived from lung ( LNM35), liver (HepG2), colon ( HT29), melanoma ( MDA- MB-435), and breast ( MDA- MB-231 and MCF-7) tumors to increasing TQ concentrations resulted in a significant inhibition of viability through the inhibition of Akt phosphorylation leading to DNA damage and activation of the mitochondrial-signaling proapoptotic pathway. We provide evidence that TQ at non-toxic concentrations inhibited the invasive potential of LNM35, MDA- MB-231, and MDA- MB231-1833 cancer cells. Moreover, we demonstrate that TQ synergizes with DNA-damaging agent cisplatin to inhibit cellular viability. The anticancer activity of thymoquinone was also investigated in athymic mice inoculated with the LNM35 lung cells. Administration of TQ (10 mg/kg/i.p.) for 18 days inhibited the LNM35 tumor growth by 39% ( P < 0.05). Tumor growth inhibition was associated with significant increase in the activated caspase-3. The in silico target identification suggests several potential targets of TQ mainly HDAC2 proteins and the 15-hydroxyprostaglandin dehydrogenase. In this context, we demonstrated that TQ treatment resulted in a significant inhibition of HDAC2 proteins. In view of the available experimental findings, we contend that thymoquinone and/or its analogues may have clinical potential as an anticancer agent alone or in combination with chemotherapeutic drugs such as cisplatin.
- Subjects
PHYTOCHEMICALS; ANTINEOPLASTIC agents; CANCER cells; TUMOR growth; DNA damage; LABORATORY mice; CISPLATIN
- Publication
Fundamental & Clinical Pharmacology, 2013, Vol 27, Issue 5, p557
- ISSN
0767-3981
- Publication type
Article
- DOI
10.1111/j.1472-8206.2012.01056.x