Induction of Apoptosis and Growth-Inhibition by Thymoquinone in ACHN and GP-293 Cell Lines in Comparable with Cis-Platinum
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objective: In the current work, we investigated the cytotoxic and apoptotic effects of Thymoquinone (TQ), an active compound of Nigella sativa (N. sativa) and Cis-platinum, on normal renal epithelial (GP-293) and human renal adenocarcinoma cell lines (ACHN). Methods: GP-293 and ACHN cell lines were cultured in Dulbecco’s modified Eagle's medium (DMEM) with 10% Fetal bovine serum (FBS) and 1% penicillin plus streptomycin antibiotic. The MTT assay was used for cellular viability assessment. Viability of cells was observed using inverted light microscope 24, 48 and 72 h after exposure of the cells to various concentrations of TQ (1, 2.5, 5, 10, 50 and 100 μg/ml) and Cis-platinum (0.5, 1, 1.5, 2, 3, 6 and 12.5 μg/ml). Moreover, apoptosis was analyzed with a flow-cytometry method. The untreated cells were considered as control group. Results: Morphological changes such as reduced cell number and increased intercellular distance and reduced cell viability in ACHN and GP-293cell lines were observed in both TQ and Cis- platinum groups; however, Cis-platinum had greater effect on ACHN cell line than GP-293 cell line. In addition, GP-293 cell line was more sensitive to TQ compared to ACHN cell line. Furthermore, TQ and Cis-platinum had apoptotic effects on both ACHN and GP-293 cell lines. Conclusion: Our findings demonstrated that TQ and Cis-platinum had cytotoxic and apoptotic effects on both cell lines, However, GP-293 cell line was more sensitive to TQ. Additionally, Cis-platinum was more effective on ACHN cell line than on GP-293 cell line.
Abstract
Objective: In the current work, we investigated the cytotoxic and apoptotic effects of Thymoquinone (TQ), an active compound of Nigella sativa (N. sativa) and Cis-platinum, on normal renal epithelial (GP-293) and human renal adenocarcinoma cell lines (ACHN). Methods: GP-293 and ACHN cell lines were cultured in Dulbecco’s modified Eagle's medium (DMEM) with 10% Fetal bovine serum (FBS) and 1% penicillin plus streptomycin antibiotic. The MTT assay was used for cellular viability assessment. Viability of cells was observed using inverted light microscope 24, 48 and 72 h after exposure of the cells to various concentrations of TQ (1, 2.5, 5, 10, 50 and 100 μg/ml) and Cis-platinum (0.5, 1, 1.5, 2, 3, 6 and 12.5 μg/ml). Moreover, apoptosis was analyzed with a flow-cytometry method. The untreated cells were considered as control group. Results: Morphological changes such as reduced cell number and increased intercellular distance and reduced cell viability in ACHN and GP-293cell lines were observed in both TQ and Cis- platinum groups; however, Cis-platinum had greater effect on ACHN cell line than GP-293 cell line. In addition, GP-293 cell line was more sensitive to TQ compared to ACHN cell line. Furthermore, TQ and Cis-platinum had apoptotic effects on both ACHN and GP-293 cell lines. Conclusion: Our findings demonstrated that TQ and Cis-platinum had cytotoxic and apoptotic effects on both cell lines, However, GP-293 cell line was more sensitive to TQ. Additionally, Cis-platinum was more effective on ACHN cell line than on GP-293 cell line.
참고문헌 (38)
- Cohen HT, "Renal-cell carcinoma", New England Journal of Medicine, 353(23), pp.2477~2490 (2005)
- Cancer Genome Atlas Research N, "Comprehensive molecular characterization of clear cell renal cell carcinoma", Nature, 499(7456), pp.43~49 (2013)
- Motzer RJ, "Renal cell carcinoma", Current problems in cancer, 21(4), pp.185~232 (1997)
- Murai M, "Renal cell carcinoma : etiology, incidence and epidemiology", Current opinion in urology, 14(4), pp.229~233 (2004)
- Madias NE, "Platinum nephrotoxicity", The American journal of medicine, 65(2), pp.307~314 (1978)
- Ali BH, "Pharmacological and toxicological properties of Nigella sativa", Phytotherapy Research, 17(4), pp.299~305 (2003)
- Boskabady MH, "Antiasthmatic effect of Nigella sativa in airways of asthmatic patients", Phytomedicine, 17(10), pp.707~713 (2010)
- Mohebbati R, "Effect of hydroalcholic extract of Nigella sativa on doxorubicin-induced functional damage of kidney in rats", The Horizon of Medical Sciences, 22(1), pp.13~20 (2016)
- Biochemical effects of Nigella sativa L seeds in diabetic rats, "Kaleem M", ~ (2006)
- Chehl N, "Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells", HPB, 11(5), pp.373~381 (2009)
- Woo CC, "Thymoquinone : potential cure for inflammatory disorders and cancer", Biochemical pharmacology, 83(4), pp.443~451 (2012)
- Ragheb A, "The protective effect of thymoquinone, an anti-oxidant and anti-inflammatory agent, against renal injury : a review", Saudi Journal of Kidney Diseases and Transplantation, 20(5), pp.741~ (2009)
- Forouzanfar F, "Black cumin(Nigella sativa)and its constituent(thymoquinone) : A review on antimicrobial effects", Iranian journal of basic medical sciences, 17(12), pp.929~ (2014)
- Das S, "Antineoplastic and apoptotic potential of traditional medicines thymoquinone and diosgenin in squamous cell carcinoma", PLoS One, 7(10), pp.e46641~ (2012)
- Rooney S, "Effects of alpha-hederin and thymoquinone, constituents of Nigella sativa, on human cancer cell lines", Anticancer research, 25(3B), pp.2199~2204 (2005)
- Shoieb AM, "In vitro inhibition of growth and induction of apoptosis in cancer cell lines by thymoquinone", International journal of oncology, 22(1), pp.107~113 (2003)
- Shahraki S, "Effect of total hydroalcholic extract of Nigella sativa and its n-hexane and ethyl acetate fractions on ACHN and GP-293 cell lines", Journal of traditional and complementary medicine, 6(1), pp.89~96 (2016)
- Tabasi N, "Cytotoxic and apoptogenic properties of Nigella sativa and thymoquinone, its constituent, in human renal cell carcinoma are comparable with cisplatin", Food and agricultural immunology, 26(1), pp.138~156 (2015)
- Ambrose M, "Induction of apoptosis in renal cell carcinoma by reactive oxygen species : Involvement of extracellular signal-regulated kinase 1", 2, p38, cyclooxygenase-2 down-regulation, and translocation of apoptosis-inducing factor, 2006, pp.69(6), 1879~1890
- Khan A, "Anticancer Activities of Nigella sativa (Black Cumin)", African Journal of Traditional, Complementary and Alternative Medicines, 8(5S) (2011)
- Yi T, "Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways", Mol Cancer Ther, 7(7), pp.1789~1796 (2008)
- Shafi G, "Induction of apoptosis in HeLa cells by chloroform fraction of seed extracts of Nigella sativa", BioMed Central, 9(29), pp.2867~2874 (2009)
- Yazan LS, "Cytotoxicity of thymoquinone (TQ) from Nigella sativa towards human cervical carcinoma cells (HeLa)", Journal of Pharmacy Research, 2(4) (2009)
- Gurung RL, "Thymoquinone induces telomere shortening, DNA damage and apoptosis in human glioblastoma cells", PloS one, 5(8), pp.e12124~ (2010)
- Gamarra-Luques CD, "Mifepristone prevents repopulation of ovarian cancer cells escaping cisplatin-paclitaxel therapy", BMC cancer, 12(1), pp.200~ (2012)
- Jafri SH, "Thymoquinone and cisplatin as a therapeutic combination in lung cancer : In vitro and in vivo", Journal of Experimental & Clinical Cancer Research, 29(87), pp.543~549 (2010)
- Arafa el SA, "Thymoquinone up-regulates PTEN expression and induces apoptosis in doxorubicin-resistant human breast cancer cells", Mutat Res, 706(1- 2), pp.28~35 (2011)
- Shoieb AM, "In vitro inhibition of growth and induction of apoptosis in cancer cell lines by thymoquinone", International journal of oncology, 10(22), pp.107~113 (2003)
- Venkatraman M, "Biological and chemical inhibitors of NF-κB sensitize SiHa cells to cisplatin-induced apoptosis", Molecular carcinogenesis, 44(1), pp.51~59 (2005)
- Burger H, "Expression of p53, Bcl-2 and Bax in cisplatin-induced apoptosis in testicular germ cell tumour cell lines", British journal of cancer, 77(10), pp.1562~ (1998)
- ZHANG RG, "Effects of cisplatin on telomerase activity and telomere length in BEL-7404 human hepatoma cells", Cell research, 12(1), pp.55~62 (2002)
- El-Mahdy MA, "Thymoquinone induces apoptosis through activation of caspase-8 and mitochondrial events in p53-null myeloblastic leukemia HL-60 cells", International journal of cancer, 117(3), pp.409~417 (2005)
- Gali-Muhtasib HU, "Molecular pathway for thymoquinone-induced cell-cycle arrest and apoptosis in neoplastic keratinocytes", Anti-cancer drugs, 15(4), pp.389~399 (2004)
- Koka PS, "Studies on molecular mechanisms of growth inhibitory effects of thymoquinone against prostate cancer cells : role of reactive oxygen species", Experimental Biology and Medicine, 235(6), pp.751~760 (2010)
- Rooney S, "Effects of alpha-hederin and thymoquinone, constituents of Nigella sativa, on human cancer cell lines", Anticancer Res, 25(3B), pp.2199~2204 (2005)
- Henkels KM, "Cisplatin-induced apoptosis proceeds by caspase-3-dependent and-independent pathways in cisplatin-resistant and-sensitive human ovarian cancer cell lines", Cancer Res, 59(13), pp.3077~3083 (1999)
- Mojab F, "Antimalarial natural products : a review", Avicenna Journal of Phytomedicine, 2(2), pp.52~62 (2012)
- Shahraki S, "Effect of aqueous fraction of Nigella sativa on percentage of live cells in human renal carcinoma cell line(ACHN)and normal human renal epithelial cells(GP-293)", Journal of North Khorasan University of Medical Sciences, 5(3), pp.585~591 (2013)
