Subscribe to RSS
DOI: 10.1055/s-0034-1372648
Luteolin Induces Apoptosis, G0/G1 Cell Cycle Growth Arrest and Mitochondrial Membrane Potential Loss in Neuroblastoma Brain Tumor Cells
Publication History
received 03 March 2014
accepted 26 March 2014
Publication Date:
15 May 2014 (online)
Abstract
The objective of the present research work was to evaluate the anticancer properties of luteolin against SH-SY5Y neuroblastoma tumor cell line. Cell viability was evaluated by MTT assay after luteolin treatment. Lactate dehydrogenase assay (LDH) was used to evaluate the extent of cell death induced by luteolin. Flow-cytometry was used to examine the effect of luteolin on cell cycle progression and mitochondrial membrane potential (ΛΨm) in SH-SY5Y cells. Phase-contrast microscopy detected the morphological changes in SH-SY5Y cells after luteolin treatment. Our results demonstrated that luteolin induced dose-dependent as well as time-dependent growth inhibition of SH-SY5Y cells with IC50 value of 27.1 µM after 12 h of incubation. Further, luteolin induced significant release of LDH from SH-SY5Y cell cultures following luteolin treatment significantly at 25 and 50 µM doses which corresponds to significant cell death. Phase-contrast microscopy revealed characteristic morphological features of apoptosis induced by luteolin. Flow-cytometry revealed that luteolin induced G0/G1 cell cycle growth arrest in SH-SY5Y cells. Luteolin also induced a progressive and dose-dependent reduction in the mitochondrial membrane potential. In conclusion, our results revealed that luteolin significantly induces growth inhibition of SH-SY5Y tumor cells by inducing apoptosis accompanied with G0/G1 cell cycle growth arrest and concomitant loss in mitochondrial membrane potential (ΛΨm). As such luteolin can be developed as a potent anticancer agent against brain tumor disorders.
* These authors contributed equally to this work.
-
References
- 1 Johnson JD, Young B. Demographics of brain metastasis. Neurosurgery Clinics of North America 1996; 7: 337-344
- 2 Posner JB. Management of brain metastases. Revue Neurologique 1992; 148: 477-487
- 3 Kim M, Bernstein M. Current treatment of cerebral metastasis. Current Opinion in Neurology 1996; 9: 414-418
- 4 Wyllie AH. Apoptosis: An overview. British Medical Bulletin 1997; 53: 451-465
- 5 Hengartner MO. The biochemistry of apoptosis. Nature 2000; 407: 770-776
- 6 Green DR, Reed JC. Mitochondria and apoptosis. Science 1998; 281: 1309-1312
- 7 Fotedar R, Diederich L, Fotedar A. Apoptosis and the cell cycle. Progress in Cell Cycle Research 1996; 2: 147-163
- 8 Johnson LV, Walsh ML, Chen LB. Localization of mitochondria in living cells with rhodamine 123. Proceedings of the National Academy of Sciences of United States of America 1980; 77: 990-994
- 9 Kayoko S, Hisae O, Michiyo F et al. FEBS Letters 438: 220-224
- 10 López-Lázaro M. Distribution and Biological Activities of the Flavonoid Luteolin. Mini-Reviews in Medicinal Chemistry 2009; 9: 31-59
- 11 Fotsis T, Pepper MS, Aktas E et al. Flavonoids, dietary-derived inhibitors of cell proliferation and in vitro angiogenesis. Cancer Research 1997; 57: 2916-2921
- 12 Kawaii S, Tomono Y, Katase E et al. Antiproliferative activity of flavonoids on several cancer cell lines. Bioscience Biotechnology and Biochemistry 1999; 63: 896-899
- 13 Post JF, Varma RS. Growth inhibitory effects of bioflavonoids and related compounds on human leukemic CEM-C1 and CEM-Cz cells. Cancer Letters 1992; 67: 207-213
- 14 Hirobe C, Qiao ZS, Takeya K et al. Cytotoxic flavonoids from Vitex agnus-castus. Phytochemistry 1997; 46: 521-524
- 15 Wang T, Zhang JC, Chen Y et al. Comparison of antioxidative and antitumor activities of six flavonoids from Epimedium koreanum. Zhongguo Zhong Yao Za Zhi 2007; 32: 715-718
- 16 Pettit GR, Hoard MS, Doubek DL. The cancer cell growth inhibitory. Constituents of Terminalia arjuna (Combretaceae). Journal of Ethnopharmacology 1996; 53: 57-63
- 17 Leung HW, Kuo CL, Yang WH et al. Antioxidant enzymes activity involvement in luteolin-induced human lung squamous carcinoma CH27 cell apoptosis. European Journal of Pharmacology 2006; 534: 12-18
- 18 Sharma V, Mishra M, Ghosh S et al. Modulation of interleukin-1beta mediated inflammatory response in human astrocytes by flavonoids: implications in neuroprotection. Brain Research Bulletin 2007; 73: 55-63
- 19 Chang H, Mi MT, Gu YY et al. Effects of flavonoids with different structures on proliferation of leukemia cell line HL-60 [Article in Chinese]. Ai Zheng 2007; 26: 1309-1314
- 20 Knowles LM, Zigrossi DA, Tauber RA et al. Flavonoids suppress androgen-independent human prostate tumor proliferation. Nutrition and Cancer 2000; 38: 116-122
- 21 Lim do Y, Jeong Y, Tyner AL et al. P. Induction of cell cycle arrest and apoptosis in HT-29 human colon cancer cells by the dietary compound luteolin. American Journal of Physiology. Gastrointestinal and Liver Physiology 2007; 292: G66-G75
- 22 Leung HW, Wu CH, Lin CH et al. Luteolin induced DNA damage leading to human lung squamous carcinoma CH27 cell apoptosis. European Journal of Pharmacology 2005; 508: 77-83
- 23 Kim JH, Lee EO, Lee HJ et al. Caspase activation and extracellular signal-regulated kinase/Akt inhibition were involved in luteolin-induced apoptosis in Lewis lung carcinoma cells. Annals of the New York Academy of Sciences 2007; 1095: 598-611
- 24 Lee HJ, Wang CJ, Kuo HC et al. Induction apoptosis of luteolin in human hepatoma HepG2 cells involving mitochondria translocation of Bax/Bak and activation of JNK. Toxicology and Applied Pharmacology 2005; 203: 124-131
- 25 Choia AY, Choia JH, Yoona H et al. Luteolin induces apoptosis through endoplasmic reticulum stress and mitochondrial dysfunction in Neuro-2a mouse neuroblastoma cells. European Journal of Pharmacology 2011; 668: 115-126
- 26 Jacobson MD, Weil M, Raff MC. Programmed cell death in animal development. Cell 1997; 88: 347-354
- 27 Golstein P. Controlling cell death. Science 1997; 275: 1081-1082
- 28 King KL, Cidlowsky JA. Cell cycle and apoptosis: common pathways to life and death. J Cell Biochemistry 1995; 58: 175-180