• 1
    Tsuruo, T., Naito, M., Tomida, A., Fujita, N., Mashima, T., et al. (2003) Molecular targeting therapy of cancer: drug resistance, apoptosis and survival signal. Cancer Sci. 94, 1521.
  • 2
    Dai, Y., Rahmani, M., Corey, S. J., Dent, P., and Grant, S. (2004) A Bcr/Abl-independent, Lyn-dependent form of imatinib mesylate (STI-571) resistance is associated with altered expression of Bcl-2. J. Biol. Chem. 279, 3422734239.
  • 3
    Lickliter, J. D., Wood, N. J., Johnson, L., McHugh, G., Tan, J., et al. (2003) HA14-1 selectively induces apoptosis in Bcl-2-overexpressing leukemia/lymphoma cells, and enhances cytarabine-induced cell death. Leukemia 17, 20742080.
  • 4
    Pei, X. Y., Dai, Y., and Grant, S. (2003) The proteasome inhibitor bortezomib promotes mitochondrial injury and apoptosis induced by the small molecule Bcl-2 inhibitor HA14-1 in multiple myeloma cells. Leukemia 17, 20362045.
  • 5
    Skommer, J., Wlodkowic, D., Matto, M., Eray, M., and Pelkonen, J. (2006) HA14-1, a small molecule Bcl-2 antagonist, induces apoptosis and modulates action of selected anticancer drugs in follicular lymphoma B cells. Leukemia Res. 30, 322331.
  • 6
    An, J., Chen, Y., and Huang, Z. (2004) Critical upstream signals of cytochrome C release induced by a novel Bcl-2 inhibitor. J. Biol. Chem. 279, 1913319140.
  • 7
    Manero, F., Gautier, F., Gallenne, T., Cauquil, N., Gree, D., et al. (2006) The small organic compound HA14-1 prevents Bcl-2 interaction with Bax to sensitize malignant glioma cells to induction of cell death. Cancer Res. 66, 27572764.
  • 8
    Milanesi, E., Costantini, P., Gambalunga, A., Colonna, R., Petronilli, V., et al. (2006) The mitochondrial effects of small organic ligands of BCL-2: sensitization of BCL-2-overexpressing cells to apoptosis by a pyrimidine-2,4,6-trione derivative. J. Biol. Chem. 281, 1006610072.
  • 9
    Zhou, Y., Hileman, E. O., Plunkett, W., Keating, M.J., and Huang, P. (2003) Free radical stress in chronic lymphocytic leukemia cells and its role in cellular sensitivity to ROS-generating anticancer agents. Blood 101, 40984104.
  • 10
    Doshi, J. M., Tian, D., and Xing, C. (2007) Ethyl-2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H- chromene-3-carboxylate (HA 14-1), a prototype small-molecule antagonist against antiapoptotic Bcl-2 proteins, decomposes to generate reactive oxygen species that induce apoptosis. Mol. Pharm. 4, 919928.
  • 11
    Halliwell, B. (1997) Ascorbic acid: hype, hoax, or healer? Am J. Clin. Nutr. 65, 18911892.
  • 12
    Nakano, H., Nakajima, A., Sakon-Komazawa, S., Piao, J. H., Xue, X., et al. (2006) Reactive oxygen species mediate crosstalk between NF-kappaB and JNK. Cell Death Differ. 13, 730737.
  • 13
    Ozben, T. (2007) Oxidative stress and apoptosis: impact on cancer therapy. J. Pharm. Sci. 96, 21812196.
  • 14
    Rushworth, S. A., Ogborne, R. M., Charalambos, C. A., and O'Connell, M. A. (2006) Role of protein kinase C delta in curcumin-induced antioxidant response element-mediated gene expression in human monocytes. Biochem. Biophys. Res. Commun. 341, 10071016.
  • 15
    Zhang, H. G., Kim, H., Liu, C., Yu, S., Wang, J., et al. (2007) Curcumin reverses breast tumor exosomes mediated immune suppression of NK cell tumor cytotoxicity. Biochim. Biophys. 1773, 11161123.
  • 16
    Ak, T. and Gulcin, I. (2008) Antioxidant and radical scavenging properties of curcumin. Chem. Biol. Interact. 174, 2737.
  • 17
    Balasubramanyam, M., Koteswari, A. A., Kumar, R. S., Monickaraj, S. F., Maheswari, J. U., et al. (2003) Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic implications. J. Biosci. 28, 715721.
  • 18
    Daniel, S., Limson, J. L., Dairam, A., Watkins, G. M., and Daya, S. (2004) Through metal binding, curcumin protects against lead- and cadmium-induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain. J. Inorg. Biochem. 98, 266275.
  • 19
    Reddy, A. C. and Lokesh, B. R. (1996) Effect of curcumin and eugenol on iron-induced hepatic toxicity in rats. Toxicology 107, 3945.
  • 20
    Chen, X., Zhong, Z., Xu, Z., Chen, L., and Wang, Y. (2011) No protective effect of curcumin on hydrogen peroxide-induced cytotoxicity in HepG2 cells. Pharmacol. Rep. 63, 724732.
  • 21
    Barzegar, A. and Moosavi-Movahedi, A. A. (2011) Intracellular ROS protection efficiency and free radical-scavenging activity of curcumin. PloS One 6, e26012.
  • 22
    Beers, R. F., Jr. and Sizer, I. W. (1952) A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J. Biol. Chem. 195, 133140.
  • 23
    Marklund, S. and Marklund, G. (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem. 47, 469474.
  • 24
    Tian, D., Das, S. G., Doshi, J. M., Peng, J., Lin, J., et al. (2008) sHA 14-1, a stable and ROS-free antagonist against anti-apoptotic Bcl-2 proteins, bypasses drug resistances and synergizes cancer therapies in human leukemia cell. Cancer Lett. 259, 198208.
  • 25
    Iqbal, M., Sharma, S. D., Okazaki, Y., Fujisawa, M., and Okada, S. (2003) Dietary supplementation of curcumin enhances antioxidant and phase II metabolizing enzymes in ddY male mice: possible role in protection against chemical carcinogenesis and toxicity. Pharmacol. Toxicol. 92, 3338.
  • 26
    Reed, J. C. (1999) Mechanisms of apoptosis avoidance in cancer. Curr. Opin. Oncol. 11, 6875.
  • 27
    Wang, J. L., Liu, D., Zhang, Z. J., Shan, S., Han, X., et al. (2000) Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc. Natl. Acad. Sci. USA 97, 71247129.
  • 28
    Reed, J. C. (1997) Bcl-2 family proteins: strategies for overcoming chemoresistance in cancer. Adv. Pharmacol. 41, 501532.
  • 29
    Kessel, D., Castelli, M., and Reiners, J. J., Jr. (2002) Apoptotic response to photodynamic therapy versus the Bcl-2 antagonist HA14-1. Photochem. Photobiol. 76, 314319.
  • 30
    Kessel, D. and Reiners, J.J., Jr. (2007) Initiation of apoptosis and autophagy by the Bcl-2 antagonist HA14-1. Cancer Lett. 249, 294299.
  • 31
    Jia, Y. L., Li, J., Qin, Z. H., and Liang, Z. Q. (2009) Autophagic and apoptotic mechanisms of curcumin-induced death in K562 cells. J. Asian Nat. Prod. Res. 11, 918928.
  • 32
    Juin, P., Geneste, O., Raimbaud, E., and Hickman, J. A. (2004) Shooting at survivors: Bcl-2 family members as drug targets for cancer. Biochim. Biophys. 1644, 251260.
  • 33
    Oltersdorf, T., Elmore, S. W., Shoemaker, A. R., Armstrong, R. C., Augeri, D. J., et al. (2005) An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature 435, 677681.
  • 34
    Kunwar, A., Sandur, S. K., Krishna, M., and Priyadarsini, K. I. (2009) Curcumin mediates time and concentration dependent regulation of redox homeostasis leading to cytotoxicity in macrophage cells. Eur. J. Pharmacol. 611, 816.
  • 35
    Gao, X., Deeb, D., Jiang, H., Liu, Y. B., Dulchavsky, S. A., et al. (2005) Curcumin differentially sensitizes malignant glioma cells to TRAIL/Apo2L-mediated apoptosis through activation of procaspases and release of cytochrome c from mitochondria. J. Exp. Therapeut. Oncol. 5, 3948.
  • 36
    Azmi, A. S., Wang, Z., Philip, P. A., Mohammad, R. M., and Sarkar, F. H. (2011) Emerging Bcl-2 inhibitors for the treatment of cancer. Exp. Opin. Emerg. Drugs 16, 5970.
  • 37
    Muppidi, J. R., Tschopp, J., Siegel, R. M. (2004) Life and death decisions: secondary complexes and lipid rafts in TNF receptor family signal transduction. Immunity 21, 461465.
  • 38
    Reddy, N. and Czuczman, M. S. (2010) Enhancing activity and overcoming chemoresistance in hematologic malignancies with bortezomib: preclinical mechanistic studies. Ann. Oncol. 21, 17561764.
  • 39
    Chen, H. W., Yu, S. L., Chen, J. J., Li, H. N., Lin, Y. C., et al. (2004) Anti-invasive gene expression profile of curcumin in lung adenocarcinoma based on a high throughput microarray analysis. Mol. Pharmacol. 65, 99110.
  • 40
    Green, D. R. and Kroemer, G. (2004) The pathophysiology of mitochondrial cell death. Science 305, 626629.
  • 41
    Notte, A., Leclere, L., and Michiels, C. (2011) Autophagy as a mediator of chemotherapy-induced cell death in cancer. Biochem. Pharmacol. 82, 427434.
  • 42
    Nyhan, M. J., O'Donovan, T. R., Elzinga, B., Crowley, L. C., O'Sullivan, G. C., et al (2012) The BH3 mimetic HA14-1 enhances 5-fluorouracil-induced autophagy and type II cell death in oesophageal cancer cells. Br. J. Cancer 106, 711718.