Introduction: Nigella sativa (NS), a dietary supplement has been investigated for its anti-oxidant, and anti-cancer activities in both in-vitro and in-vivo models. We hypothesized that NS oil can inhibit lung cancer tumor growth in-vivo.
Methods: Twenty, 5-6 weeks old SCID/bg (severe combined immune deficiency) mice were injected with 2×106 non-small cell lung cancer cell line (NCI-H460) in the right flank. Mice were randomized to receive Canola oil (n=10, control) or Nigella sativa (NS) oil (n=10, treatment) by oral gavage 0.1ml per dose (5ml/kg) daily Monday through Friday. Tumor volume was measured twice a week. Mice were sacrificed at Day 28 and tumors harvested at necropsy. Determination activities of glutathione reductase (GR), glutathione-S-transferase (GST), glucose-6-phosphate dehydrogenase (G6PDH), catalase (Cat), lactate dehydrogenase (LDH), content of reduced glutathione (GSH) were analyzed using spectrophotometry methods and calculated relative to the amount of total protein in the samples. The results of specific activities of enzymes, content GSH and tumor volumes were analyzed with Student's t-test and Spearman's correlation coefficient. Tumor growth inhibition ratio (T/C ratio) was defined as the ratio of tumor volume between treatment and control group to assess the effect NS oil on tumor growth.
Results: Tumors developed within a week of injecting cells. Overall T/C ratio by NS oil was 75%. Mean tumor volume of control group on Day 28 was 1992.7 mm3 and that of treatment group was 1432.9 mm3 (p=0.25). Tumor inhibition was noticed to be more prominent on Fridays (T/C ratio=0.66) in comparison with Mondays (T/C ratio=0.75) suggesting chronic daily treatment would be more likely to produce a sustained response. Examination of the specific enzymatic activities in tumors of the mice, which were treated with NS oil in comparison with control group show decrease GR (74.9%), GST (82.6%), Cat (57.2%), and non-sufficient increasing G6PDH (118%) and LDH (120%) were shown. GSH content within the NS oil treatment group was decreased by 90.9%. Spearman's correlation analysis indicated a strong positive interrelation between GR and G6PDH in the tumors of control mice (r=+0.804, p<0.025), but interrelation between these enzymes in tumors of mice treated with NS oil did not show as much (r=+0.350, p>0.05), and this demonstrated an imbalance between these enzymes. Pathological examination of tumor samples from both groups showed extensive necrosis more prominent in NS treated tumors.
Conclusion: This study clarified the role of NS oil ingredients as anti-oxidants in modulation of anti-oxidative enzymes activities, which play an important protective role in the intra-cellular defense system and regulation of tumor progression. NS oil slows down lung cancer growth, which is quite remarkable for a dietary supplement, and may show additional benefit when added to other anti-cancer drugs.
Citation Format: Kevin Gallagher, Syed Jafri, Reinhold Munker, Glenn Mills, Jennifer Minadeo, Heather Kleiner - Hancock, Misty Prince, Ludmila Gavriliuc, Shubnum Chaudhery, Catherine Chaudoir, Runhua Shi. Nigella sativa oil affects lung cancer growth and modulates anti-oxidant enzymes in a mouse xenograft model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3132. doi:10.1158/1538-7445.AM2014-3132