Category Archives: MDA-MB-231 and MCF-7

A431, Akt, Anti-cancer, anti-inflammatory, anti-proliferative, apoptosis, Apoptotic, Bcl-2, Breast cancer, cell-cycle arrest, Chapter 7 Isolates and Cancer Research, Colon Cancer or Colorectal cancer, COX-2, G1, HCT-116, Hep2, HepG2, HT29, induces apoptosis, Induces cell-cycle arrest, inflammation, inhibits proliferation, Liver cancer, LNM35, MCP-1, MDA-MB-231 and MCF-7, MDA-MB-435, Melanoma, Nigella sativa, Osteosarcoma, p21, p53, Pancreatic cancer, Pro-apoptotic, Saos-2, Sarcoma, TNF

Thymoquinone

Cancer: Osteosarcoma, pancreatic, colorectal., lung, liver, melanoma, breast

Action: Anti-inflammatory

For centuries, the black seed (Nigella sativa (L.)) herb and oil have been used in Asia, Middle East and Africa to promote health and fight disease. Thymoquinone (TQ) is the major phytochemical constituent of Nigella sativa (L.) oil extract. Phytochemical compounds are emerging as a new generation of anti-cancer agents with limited toxicity in cancer patients.

Osteosarcoma

The anti-proliferative and pro-apoptotic effects of TQ were evaluated in two human osteosarcoma cell lines with different p53 mutation status. TQ decreased cell survival dose-dependently and, more significantly, in p53-null MG63 cells (IC(50) = 17 muM) than in p53-mutant MNNG/HOS cells (IC(50) = 38 muM). Cell viability was reduced more selectively in MG63 tumor cells than in normal human osteoblasts.

It was therefore suggested that the resistance of MNNG/HOS cells to drug-induced apoptosis is caused by the up-regulation of p21(WAF1) by the mutant p53 (transcriptional activity was shown by p53 siRNA treatment) which induces cell-cycle arrest and allows repair of DNA damage.

Collectively, these findings show that TQ induces p53-independent apoptosis in human osteosarcoma cells. As the loss of p53 function is frequently observed in osteosarcoma patients, these data suggest the potential clinical usefulness of TQ for the treatment of these malignancies (Roepke et al., 2007).

Pancreatic Ductal Adenocarcinoma

Inflammation has been identified as a significant factor in the development of solid tumor malignancies. It has recently been shown that thymoquinone (Tq) induces apoptosis and inhibited proliferation in PDA cells. The effect of Tq on the expression of different pro-inflammatory cytokines and chemokines was analyzed by real-time polymerase chain reaction (PCR). Tq dose- and time-dependently significantly reduced PDA cell synthesis of MCP-1, TNF-alpha, interleukin (IL)-1beta and Cox-2. Tq also inhibited the constitutive and TNF-alpha-mediated activation of NF-kappaB in PDA cells and reduced the transport of NF-kappaB from the cytosol to the nucleus. Our data demonstrate previously undescribed anti-inflammatory activities of Tq in PDA cells, which are paralleled by inhibition of NF-kappaB. Tq as a novel inhibitor of pro-inflammatory pathways provides a promising strategy that combines anti-inflammatory and pro-apoptotic modes of action (Chehl et al., 2009).

Lung cancer, Hepatoma, Melanoma, Colon Cancer, Breast Cancer

The potential impact of thymoquinone (TQ) was investigated on the 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 pro-apoptotic pathway. 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. In this context, it has been demonstrated that TQ treatment resulted in a significant inhibition of HDAC2 proteins. In view of the available experimental findings, it is contended that thymoquinone and/or its analogues may have clinical potential as an anti-cancer agent alone or in combination with chemotherapeutic drugs such as cisplatin (Attoub et al., 2012).

Colon Cancer

It was reported that TQ inhibits the growth of colon cancer cells which was correlated with G1 phase arrest of the cell-cycle. Furthermore, TUNEL staining and flow cytometry analysis indicate that TQ triggers apoptosis in a dose- and time-dependent manner. These results indicate that TQ is anti-neoplastic and pro-apoptotic against colon cancer cell line HCT116. The apoptotic effects of TQ are modulated by Bcl-2 protein and are linked to and dependent on p53. Our data support the potential for using the agent TQ for the treatment of colon cancer (Gali-Muhtasib et al., 2004).

References

Attoub S, Sperandio O, Raza H, et al. (2012). Thymoquinone as an anti-cancer agent: evidence from inhibition of cancer cells viability and invasion in vitro and tumor growth in vivo. Fundam Clin Pharmacol, 27(5):557-569. doi: 10.1111/j.1472-8206.2012.01056.x


Chehl N, Chipitsyna G, Gong Q, Yeo CJ, Arafat HA. (2009). Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells. HPB (Oxford), 11(5):373-81. doi: 10.1111/j.1477-2574.2009.00059.x.


Gali-Muhtasib H, Diab-Assaf M, Boltze C, et al. (2004). Thymoquinone extracted from black seed triggers apoptotic cell death in human colorectal cancer cells via a p53-dependent mechanism. Int J Oncol, 25(4):857-66


Roepke M, Diestel A, Bajbouj K, et al. (2007). Lack of p53 augments thymoquinone-induced apoptosis and caspase activation in human osteosarcoma cells. Cancer Biol Ther, 6(2):160-9.