Multidrug tumor cells

The development of chemotherapeutic agents for the treatment of cancer has resulted in a significant number of once fatal neoplasia to become classified as curable, or at the very least, treatable. However, despite the great advances in the synthesis of new anti-cancer compounds, these compounds tend to possess nonspecific toxicity restricting their efficiency in vivo. Furthermore, multidrug tumor cell resistance is fairly common. 

One interesting example of the potential importance of intracellular pH gradients is found in the phenomenon of multidrug resistance (MDR). The MDR protein acts as a molecular pump, actively pumping chemotherapeutic agents out of the cell. Tumor cells, which are susceptible to chemotherapeutics have often a lower intracellular pH [178], which would lead to enhanced accumulation of these drugs in response to the pH differ-... 

Ganta, S. and Amiji, M. (2009) Coadministration of paclitaxel and curcumin in nanoemulsion formulations to overcome multidrug resistance in tumor cells. Molecular Pharmacology, 6 (3), 928-939. Sonneville-Aubrun, O., Simonnet, J.-T. and L Alloret, F. (2004) Nanoemulsions a new vehicle for skincare products. Advances in Colloid and Interface Science, 108-109, 145-149. 

Raviv, Y., Pollard, H. B., Bruggemann, E. P., Pastan, I., Gottesman, M. M., Photosensitized labeling of a functional multidrug transporter in living drug-resistant tumor cells, J. Biol. Chem. 1990, 265, 3975-3980. 

As described in several monographs [4], bryostatin 1 exhibits significant in vitro and in vivo antineoplastic activity against a range of tumor cell lines including murine leukemia, B-cell lymphoma, reticulum cell sarcoma, ovarian carcinoma, and melanoma. It is also effective in the modulation of apoptotic function [5], the reversal of multidrug resistance [6], and stimulation of the immune system [7]. These unique features displayed by bryostatin 1 are attributed to its high affinity for protein kinase C (PKC) isozymes and its ability to selectively modulate their functions [8]. PKCs are a type of intracellular serine and threonine kinase that... 

Chemical Synthesis and Biological Studies of the Epothilones - Microtubule Stabilizing Agents with Enhanced Activity Against Multidrug-Resistant Cell Lines and Tumors. 

Cyclopamine also interferes with cholesterol metabolism that results in decreased cholesterol synthesis and the accumulation of late biosynthetic intermediates. Cyclopamine was evaluated as an inhibitor of multi-drug resistance in tumor cells. Intrinsic or acquired resistance of tumor cells to cytotoxic drugs is a major cause of failure of chemotherapy. Both cyclopamine and the spirosolane alkaloid tomatidine from tomatoes act as potent and elfective chemosensitizers in multidrug-resistant cells (Lavie et ah, 2001). Therefore, plant steroidal alkaloids, such as cyclopamine and tomatidine, or their analogs, may serve as chemosensitizers in combination with chemotherapy and conventional cytotoxic drugs for treating multidrug-resistant cancers. 

Meschini, S., Marra, M., Condello, M., Calcabrini, A., Federici, E., Dupuis, M. L., Cianfriglia, M. and Arancia, G. 2005. Voacamine, an alkaloid extracted from Peschiera fuchsiaefolia, inhibits P-glycoprotein action in multidrug-resistant tumor cells. International Journal of Oncology, 27(6) 1597-1603. 

Dactinomycin (actinomycin D, Cosmegen) is one of a family of chromopeptides produced by Streptomyces. It is known to bind noncovalently to double-strand DNA by partial intercalation, inhibiting DNA-directed RNA synthesis. The drug is most toxic to proliferating cells, but it is not specific for any one phase of the cell cycle. Resistance to dactinomycin is caused by decreased ability of tumor cells to take up and retain the drug, and it is associated with cross-resistance to vinca alkaloids, the anthracyclines, and certain other agents (multidrug resistance). 

The major mechanism of resistance that has been identified for paclitaxel is transport out of tumor cells, which leads to decreased intracellular drug accumulation. This form of resistance is mediated by the multidrug transporter P-glycoprotein. 

Dendrilla cactos, Dendroc., Porif. from Bass Strait, S Australia/cytotoxic on multidrug resistant tumor cells... 

Elkind NB, Szentpetery Z, Apati A et al. Multidrug transporter ABCG2 prevents tumor cell death induced by the epidermal growth factor receptor inhibitor Iressa (ZD1839, gefitinib). Cancer Res... 

Kobayashi, H., Dorai, T., Holland, J.F. and Ohnuma, T. (1994) Reversal of drug sensitivity in multidrug-resistant tumor cells by an MDR1 (PGYl)ribozyme. Cancer Res., 54, 1271-1275. 

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