The phosphatidylinositol 3-kinase (PI3K)/serine-theronine protein kinase Akt is a vital signaling cascade involved in cell survival, progression and thus causes various types of cancers. Various kinase inhibitors targeting PI3K/Akt have been extensively studied but promising results could not be obtained because of toxicity and resistance issues. The aim of present study was to analyze the interaction of plant derived natural moieties such as nimbin, cannabidiol and acetogenin to PI3K and Akt signaling molecules. Results showed that nimbin, cannabidiol and acetogenin significantly binds to both signaling molecules. They revealed almost equivalent potency of binding to PI3K at their respective active site but nimbin exhibited lower free energy of binding with Akt. A combinational drug therapy comprises of these natural metabolites that can target these specific protein kinases efficiently can prove as a boon for breast and other cancers treatment.
<p><strong>Objective: </strong>Main aim of the present study was to determine differential effects of temperature and pH on the sensitivity/resistance of bacteria against ciprofloxacin and chloramphenicol.</p><p><strong>Methods: </strong>Both the bacterial strains were subjected to MIC determination. These were subjected to the varying values of environmental stresses including temperature and pH. The growth was monitored using spectrophotometer and degree of resistance if gained was screened over the agar dilution plates. Morphological changes were also observed in the shape and size of bacteria using light microscope at 1000X.<strong></strong></p><p><strong>Results: </strong>Present study enlightened the facts that pathogenic strain and a non-pathogenic strain of <em>E. coli</em> behave differently for factors like pH and temperature. It is not so that if non-pathogenic <em>E. coli</em> gains resistance to antibiotic under a specified condition of temperature and pH, then the pathogenic strain would also gain resistance the same way. It was noticed in present study that non-pathogenic <em>E. coli</em> is not very sensitive to the antibiotics, but the pathogenic <em>E. coli</em> is much more sensitive to antibiotics like ciprofloxacin, however it is easy for the pathogenic strain than the non-pathogenic one to gain resistance to antibiotic if proper environmental condition is made available like temperature of 30 °C and pH 6.5 (which appeared to be the best value of respective stresses regarding gain of resistance). However, it is not so that two drugs like ciprofloxacin and chloramphenicol acts with efficacy in similar environmental conditions. Similarly, the bacteria also gains resistance to these drugs under different environmental conditions. The study proved pivotal in concluding that temperature alone can’t induce resistance in the bacteria against the antibiotic, also pH plays more significant role in the efficacy of antibiotic and the resistance acquired against it.</p><p><strong>Conclusion: </strong>Both pathogenic and non-pathogenic strains of <em>E. coli</em> behave differently against the abiotic stresses and there may exist a different mechanism of stress regulation in both the strains, which may get even more complicated if the combination of stresses are taken into consideration. These points may help us to understand and get a permanent solution for antibiotic resistance of bacteria hence making pathogens sensitive and non-pathogenic/useful bacteria resistant to the antibiotics.<strong></strong></p>
Estrogens along with their receptors are required for the normal physiological development of women. However, in altered physiological conditions a high level of estrogens acts either as initiator or progressor of breast cancer. Approximately in 75% of estrogen dependent breast cancer cases estrogen receptors (ERs) are held responsible. Recent studies indicate that estrogens along with iron (Fe) concomitantly involved in the proliferation of ER(+) breast cancer cells. While a number of antiestrogen/anti-ER drugs including selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs) and selective estrogen receptor down regulators (SERDs) are used to eradicate breast cancer but their action on Fe dependent breast cancer complication is not yet explored. Moreover, many of the ER(+) breast cancer patients receiving anti-estrogen drugs relapsed within a couple of years and become resistant to antiestrogen therapy. Mutation and loss of affinity to the target molecule (ERs), loss or overexpression of ERs, along with activation of growth promoting pathways alternative to estrogen-ER pathways are the major reasons of drug resistance. Combinational therapy may be best alternative to antiestrogen relapsed patients. Some of the widely studied drug combinations are roscovitine (ROSC) and tamoxifen, metformin and tamoxifen, tamoxifen and RAD001. While in all these drug combinations anti-ER compound tamoxifen may be one of the major content, anti-Fe compounds are yet to be used as drug combination. The present review article describes all the currently studied drugs/drug combinations in ER(+) breast cancer cells and future drug possibilities including anti-Fe compounds.
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