Drug and Alcohol Rehabilitation: Adva-27a, a Novel Podophyllotoxin Derivative Found to Be Effective Against Multidrug Resistant Human Cancer Cells.

Adva-27a, a Novel Podophyllotoxin Derivative Found to Be Effective against Multidrug Resistant Human Cancer Cells.

Filed under: Drug and Alcohol Rehabilitation

Anticancer Res. 2012 Oct; 32(10): 4423-32
Merzouki A, Buschmann MD, Jean M, Young RS, Liao S, Gal S, Li Z, Slilaty SN

Background/Aim: Multidrug resistance poses a serious challenge in cancer therapy. To address this problem, we designed and synthesized Adva-27a, a novel non-ester GEM-difluorinated C-glycoside derivative of podophyllotoxin.Adva-27a activity was evaluated in a variety of assays including inhibition of topoisomerase II?, cytotoxic activity in drug-sensitive and drug-resistant cancer cell lines, metabolic stability in human liver microsomes and pharmacokinetic properties in rats.Adva-27a exhibited dose-dependent human topoisomerase II? inhibitory activity and dose-dependent growth inhibitory activity in several drug-sensitive and two multidrug-resistant cancer cell lines. In the multidrug-resistant cell lines, MCF-7/MDR (breast cancer) and H69AR (small-cell lung cancer), Adva-27a was significantly more potent than etoposide. The metabolic stability of Adva-27a in human liver microsomes and its pharmacokinetic properties in rats were better than those of etoposide.Our studies have identified Adva-27a as a novel topoisomerase II inhibitor with superior cytotoxic activity against multidrug-resistant human cancer cells and more desirable pharmacokinetic properties than etoposide.
HubMed – drug


Kinase Inhibition by the Jamaican Ball Moss, Tillandsia recurvata L.

Filed under: Drug and Alcohol Rehabilitation

Anticancer Res. 2012 Oct; 32(10): 4419-22
Lowe HI, Watson CT, Badal S, Toyang NJ, Bryant J

This research was undertaken in order to investigate the inhibitory potential of the Jamaican ball moss, Tillandsia recurvata against several kinases. The inhibition of these kinases has emerged as a potential solution to restoring the tight regulation of normal cellular growth, the loss of which leads to cancer cell formation.Kinase inhibition was investigated using competition binding (to the ATP sites) assays, which have been previously established and authenticated.Four hundred and fifty one kinases were tested against the Jamaican ball moss extract and a dose-response was tested on 40 kinases, which were inhibited by more than 35% compared to the control. Out of the 40 kinases, the Jamaican ball moss selectively inhibited 5 (CSNK2A2, MEK5, GAK, FLT and DRAK1) and obtained Kd(50)s were below 20 ?g/ml.Since MEK5 and GAK kinases have been associated with aggressive prostate cancer, the inhibitory properties of the ball moss against them, coupled with its previously found bioactivity towards the PC-3 cell line, makes it promising in the arena of drug discovery towards prostate cancer.
HubMed – drug


Synergism in Concomitant Chemoradiotherapy of Cisplatin and Oxaliplatin and their Liposomal Formulation in the Human Colorectal Cancer HCT116 Model.

Filed under: Drug and Alcohol Rehabilitation

Anticancer Res. 2012 Oct; 32(10): 4395-404
Tippayamontri T, Kotb R, Paquette B, Sanche L

We choose to test the effect of associating chemo-radiotherapy at 8 h (the highest level of DNA-platinum) and 48 h (the lower level of DNA-platinum) to clarify if irradiation at the maximum DNA-platinum concentration could improve the synergism.Growth inhibition of the human colorectal cancer cell line HCT116 treated with cisplatin, oxaliplatin, Lipoplatin™ and Lipoxal™ plus gamma-radiation was determined by a colony formation assay. The synergism was evaluated using the combination index method.For 8 h and 48 h exposure to cisplatin or Lipoplatin™, followed by irradiation, drug concentrations higher than IC(50) were found to be synergistic, while a lower than IC(50) concentration was antagonistic. For oxaliplatin, exposure to a concentration above IC(50) for 8 h was synergistic, while the exposure to oxaliplatin (at any concentrations) for 48 h was antagonistic. Lipoxal™ significantly improved synergism compared to its parent drugs. All tested platinum drugs sensitize radiation-treated HCT116 cells by inducing G(2) phase.The difference of drug concentrations and the time interval between drug administration and radiotherapy could give different results in chemoradiation therapy.
HubMed – drug



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