Abstract
Resveratrol, a phytoalexin found in the skin of grapes, is believed to have multiple bioactivities including anti-cancer, anti-carcinogenesis and antiinflammatory. The mechanisms by which resveratrol might produce these effects are not well understood. In this study, malignant human pancreatic cancer cells were treated without or with resveratrol in combination with ionizing radiation (IR), and then the mitochondrial function of treated cells was evaluated using several standardized assays. They include the CalceinAMmethod for mitochondria transition pore; the JC-1 staining method for mitochondria membrane potential; the CM-H2DCFDA method for reactive oxygen species; and the Annexin V/propidium iodide (PI) method for apoptosis/cell death. Our results indicated that (1) pore function was partially intact after resveratrol, but resveratrol probably interfered with the accumulation of intracellular Calcein AM; (2) depolarization of the mitochondria membrane was increased in the resveratrol treated cells, consistent with mitochondrial dysfunction; (3) ROS was slightly increased with resveratrol, a phenomenon that was greatly increased when this agent was combined with IR; and (4) in parallel with the above changes in mitochondrial and drug transport, cells treated with resveratrol showed increased apoptosis as measured by Annexin V/PI staining. In summary, the anti-cancer effect of resveratrol is associated with the damage of mitochondrial function that leads to increased ROS, apoptosis, and possibly intracellular drug accumulation via inhibition of proteins involved in multi-drug resistance (MDR).
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References
P. Waffo-Teguo, M. E. Hawthorne, M. Cuendet, et al., Potential cancer-chemopreventive activities of wine stilbenoids and flavans extracted from grape (Vitis vinifera) cell cultures, Nutr. Cancer 40(2):173–179 (2001).
L. Fremont, Biological effects of resveratrol, Life Sci. 66(8):663–673 (2000).
G. J. Soleas, and E. P. Diamandis, and D. M. Goldberg, Resveratrol: a molecule whose time has come? And gone? Clin. Biochem. 30(2):91–113 (1997).
J. K. Lin, and S. H. Tsai, Chemoprevention of cancer and cardiovascular disease by resveratrol, Proc. Natl. Sci. Coun. Repub. China B. 23(3), 99–106 (1999).
J. A. Baur, and D. A. Sinclair, Therapeutic potential of resveratrol: the in vivo evidence, Natl. Rev. Drug Discov. 5(6), 493–506 (2006).
S. K. Manna, A. Mukhopadhyay, and B. B. Aggarwal, Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappa B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation, J. Immunol. 164(12), 6509–6519 (2000).
S. Pervaiz, Resveratrol–from the bottle to the bedside? Leuk. Lymphoma. 40(5–6), 491–498 (2001).
S. Fulda, and K. M. Debatin, Resveratrol modulation of signal transduction in apoptosis and cell survival: A mini-review, Cancer Detect. Prev. 30(3), 217–223 (2006).
D. Delmas, A. Lancon, D. Colin, B. Jannin, and N. Latruffe, Resveratrol as a chemopreventive agent: a promising molecule for fighting cancer, Curr. Drug Targets 7(4), 423–442 (2006).
http://probes.invitrogen.com/media/publications/508.pdf http://probes.invitrogen.com/media/publications/508.pdf
N. Dias, and C. Bailly, Drugs targeting mitochondrial functions to control tumor cell growth, Biochem. Pharmacol. 70(1):1–12 (2005).
R. Kim, Recent advances in understanding the cell death pathways activated by anticancer therapy, Cancer 103(8):1551–1560 (2005).
T. Asakura, and K. Ohkawa, Chemotherapeutic agents that induce mitochondrial apoptosis, Curr. Cancer Drug Targets 4(7):577–590 (2004).
S. Eisold, D. Nauheimer, J. Schmidt, T. Giese, E. Klar, and M. Linnebacher, Influence of clinically relevant chemotherapeutics on the expression of multidrug-resistance family members in human pancreatic cell lines, Society for Surgery of the Alimentary Tract [abstract]; accessed online 21Dec2006: http://www.ssat.com/cgi-bin/abstracts/06ddw/SSAT_DDW06_38.cgihttp://www.ssat.com/cgi-bin/abstracts/06ddw/SSAT_DDW06_38.cgi
S. J. Zunino, and D. H. Storms, Resveratrol-induced apoptosis is enhanced in acute lymphoblastic leukemia cells by modulation of the mitochondrial permeability transition pore, Cancer Lett. 240(1), 123–134 (2005).
X. M. Tian, and Z. X. Zhang ZX, Resveratrol promote permeability transition pore opening mediated by Ca2+, Yao. Xue. Xue. Bao. 38(2), 81–84 (2003).
C. Huang, W. Y. Ma, A. Goranson, and Z. Dong, Resveratrol suppresses cell transformation and induces apoptosis through a p53-dependent pathway, Carcinogenesis 20(2), 237–242 (1999).
J. F. Moreno-Labanda, R. Mallavia, L. Perez-Fons, V. Lizama, D. Saura, and V. Micol, Determination of piceid and resveratrol in Spanish wines deriving from Monastrell (Vitis vinifera L.) grape variety, J Agric Food Chem. 52(17), 5396–5403 (2004).
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Sun, W. et al. (2008). Anti-Cancer Effect of Resveratrol is Associated with Induction of Apoptosis via a Mitochondrial Pathway Alignment. In: Kang, K.A., Harrison, D.K., Bruley, D.F. (eds) Oxygen Transport to Tissue XXIX. Advances In Experimental Medicine And Biology, vol 614. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-74911-2_21
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DOI: https://doi.org/10.1007/978-0-387-74911-2_21
Publisher Name: Springer, Boston, MA
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