Cancer cells, accumulation

CD, as produced by breast cancer cells in vitro, can exist in multiple molecular-weight forms. It is initially synthesized as an Mt 52,000 protein. This precursor protein is transported to lysosomes, where it is processed to an intermediate 48-kDa protein. The 48-kDa form is later converted into mature forms with molecular weights of 34,000 and 14,000 (R3). Processing of CD appears to be slower in cancer cells than in normal cells (R3). As a result, cancer cells accumulate greater proportions of the 52 kDa and 48 kDa forms than do nonmalignant cells (R3). 

Kam et al. [38-40] SW CNT-r cytochrome C,RNA, DNA CNT transferred cytochrome C to the cancer cells accumulation of SW CNT-RNA conjugates in cytoplasm and nucleus of HeLa cells... 

In the NF-kB pathway with celastrol 76, the inhibition of the iKBa degradation is due to the upstream blockage of the kinase activity and not by the direct inhibition of proteasome activity. On the contrary, direct inhibition of proteasome activity was observed with celastrol 76 and pristimerin 2 in prostate cancer cells.90-92 Both triterpene QMs directly inhibited the activity of the 20S subunits of proteasome at 2.5 iM and induced the accumulation of ubiquitinated proteins over time in cells,... 

The involvement of mitochondria in the pro-apoptotic effects of carotenoids has been clearly demonstrated by the fact that P-carotene induces the release of cytochrome c from mitochondria and alters the mitochondrial membrane potential (Aym) in different tumor cells (Palozza et al., 2003a). Moreover, the highly polar xanthophyll neoxanthin has been reported to induce apoptosis in colon cancer cells by a mechanism that involves its accumulation into the mitochondria and a consequent loss of mitochondrial transmembrane potential and releas of cytochrome c and apoptosis-inducing factor (Terasaki et al., 2007). 

Kawakami, M., Kagotani, K., Okumura, K., Akiyama, S., Kuwano, M., A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation, Cancer Res. 1996, 56, 4124-4129. 

EGER targeting was also used for systemic delivery of pDNA expressing the sodium iodide symporter (NIS) gene to liver cancer cells, followed by administration of radioactive isotope iodine-131, which accumulates in the tumor by NIS-mediated uptake in radiotherapeutic doses [227]. 

Sensitivity of cancerous cells to copper may reflect cell DNA content. Two closely related rat hepatoma cell lines differed in sensitivity to copper toxicity by a factor of four DNA content in each cell line decreased with increasing copper concentrations, but at different rates. Severity of toxicity was associated with increasing accumulations of copper in the cell nucleus and with decreasing DNA (Toussaint and Nederbragt 1993). 

P-gp is expressed in tumor tissue and serves as a barrier to increased accumulation of cytotoxic anticancer drugs within the cancer cell by actively pumping the drug out of the cell. It is a multidrug resistance element by virtue of the fact that it is promiscuous in terms of substrate selectivity. It, like the cytochromes P450, will accept a wide diversity of structural types. For example, a small sampling of drugs that are substrates for P-gp... 

Ma I, Maliepard M, Nooter K, Loos WJ, Kolker HJ, Verweij J, Stoter G, Schellens JHM (1998b) Reduced cellular accumulation of topotecan a novel medianism of resistance in a human ovarian cancer cell line. Br ) Cancer 77 1645-1652 MacFarlane DE, O Donnell PS (1993) Phorbol ester induces apoptosis in HL-60 promyelocytic leukemia cells but not in HL-60 PET mutant. Leukemia 7 1846-1851... 

Fig. 3. Mechanism of synthetic lethality between PARP inhibition and BRCA deficiency. PARP inhibition blocks the activity of BER and leads to DNA SSB accumulation inside cells. When cells enter the next round of DNA replication, these DNA SSBs are converted to DNA DSBs which can be efficiently repaired through the HR pathway in normal cells. BRCA deficient cancer cells are unable to repair the DNA DSBs that accumulate following PARP inhibition. This eventually causes toxicity and cancer cell death.

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