Apoptosis inducing activity

Chowdhury SA et al (2005) Tumor-specificity and apoptosis-inducing activity of stilbenes and flavonoids. Anticancer Res 25(3B) 2055-2063... 

Structure-activity relationship in apoptosis inducing activity... 

Turos and Ping found that two (3-lactam analogs (73 and 74), both containing a branched-chain system at C3 of the ring, exhibited potent apoptosis-inducing activity. However, 73 exhibited superior in vitro activity over 74. (Fig. 3) The (3-lactams with these side chains were able to inhibit the growth of mice bearing... 

Kikuchi K, Shima H, Mitsuhashi S, Suzuki M, Oikawa H (1999) The Apoptosis-Inducing Activity of the Two Protein Phosphatase Inhibitors, Tautomycin and Thyrsiferyl 23-Ace-tate, is not due to the Inhibition of Protein Phosphatases PP1 and PP2A (Review). Int J Mol Med 4 395... 

Yui S, Nakatani Y, Hunter MJ, Chazin WJ, Yamazaki M. 2002. Implication of extracellular zinc exclusion by recombinant human calprotectin (MRP8 and MRP14) from target cells in its apoptosis-inducing activity. Mediators Inflamm 11(3) 165-172. 

MK-2 induced apoptosis to a much lesser extent than GG. The major difference between MK-2 and GG is the u,(J>-unsaluraled ketone structure present in MK-2 but not in GG. The induction of cell death by MK-2 or GG was not coupled with radical generation. It has recently been reported that the induction of apoptosis by MK-4 in human ovary cancer cells is mediated by oxidative stress in mitochondria [70]. Since autophagy plays an important role in reducing mitochondrial damage and reactive oxygen species, there is a possibility that the apoptosis-inducing activity of MK-4 may be derived from the inhibition of autophagy. 

Heterocycles such as 4-trifluoromethylimidazole, phenoxazine, 3-formyl-chromone, coumarin derivatives, and vitamin K2 derivatives were investigated for their cytotoxicity against human normal and tumor cells. These compounds induced moderate tumor-specific cytotoxicity. VitaminK2 derivatives and prenylalcohols displayed disappointingly low tumor-specific cytotoxicity, although they have been reported to induce apoptosis-inducing activity. Human oral squamous cell carcinoma cell lines showed considerable variation in drug sensitivity. The type of cell death induced depended both on which types of cells and which inducers were used. 

The same group has also repotted a multicomponent Hantzsch protocol which provided access to polycyclic indenoheterocycles 78 utilizing a variety of aromatic and heterocyclic amines (Scheme 19) [45]. Some of the compounds disclosed showed apoptosis-inducing activity in a human T-cell leukemia cell line similar to etoposide. One of the most potent analogs was compound 79 (Scheme 19) which showed greater than 30% induction of apoptosis at 25 pM, as assessed in a flow cytometric aimexin V/propidium iodide assay in Jurkat cells. 

Itoh, M., Kuwahara, J, Itoh, K., Fukuda, Y, Kohya, M., Shindo, M. and Shishido, K., 2002. Apoptosis-inducing activity of synthetic intermediates ofhalichlorine. BioorgMed Chem Lett 12, 2069-2072. 

Anthocyanins are a proanthocyanidin-type of flavonoid distributed in various fruits. These anthocyanins are the most important visible plant pigments in the natural kingdom. Anthocyanins have been clinically used in many folklore medicines worldwide for the treatment of age-related diseases and other disease. This review presents the functionality of anthocyanins in relation to their chemistry, synthetic pathway, antioxidant activity, antitumor activity (including apoptosis-inducing activity), pharmacodynamics (absorption, metabolism, distribution, and excretion) and toxicity, and discusses their possible use as food and dietary supplements and usage in potential nutraceuticals. 

The compounds from the ethyl acetate fraction showing strong apoptosis-inducing activity were identified by spectral methods as epidioxysterols. The in vitro results suggest that induction of apoptosis by epidioxysterols may provide a pivotal mechanism for its cancer chemoprevention. 

On the other hand, the trienomycins A (111) - C (113) were reported to have potent cytocidal activities [169,171,175] and antitumor activity was reported for trienomycin A (111) [236]. Cytotrienins A (104) and B (105) were isolated from the culture broth of Streptomyces sp., and these compounds exhibit potent apoptosis-inducing activity on human leukemia HL-60 cells with ED50 values of 7.7 nM, which were the same dose range as for their growth inhibitory activities [165-167]. 

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