Modulation of septin and molecular motor recruitment in the microtubule environment of the Taxol‐resistant human breast cancer cell line MDA‐MB‐231

Abstract

Cell resistance to low doses of paclitaxel (Taxol) involves a modulation of microtubule (MT) dynamics. We applied a proteomic approach based on 2-DE coupled with MS to identify changes in the MT environment of Taxol-resistant breast cancer cells. Having established a proteomic pattern of the microtubular proteins extracted from MDA-MB-231 cells, we verified by Western blotting that in resistant cells, α- and β-tubulins (more specifically the βIII and βIV isotypes) increased. Interestingly, four septins (SEPT2, 8, 9 and 11), which are GTPases involved in cytokinesis and in MT/actin cytoskeleton organization, were overexpressed and enriched in the MT environment of Taxol-resistant cells compared to their sensitive counterpart. Changes in the MT proteome of resistant cells also comprised increased kinesin-1 heavy chain expression and recruitment on MTs while dynein light chain-1 was downregulated. Modulation of motor protein recruitment around MTs might reflect their important role in controlling MT dynamics via the organization of signaling pathways. The identification of proteins previously unknown to be linked to taxane-resistance could also be valuable to identify new biological markers of resistance.

Purification and differential biological effects of ginger-derived substances on normal and tumor cell lines

“…In this work, the authors isolated the major gingerols from the crude dichloromethane extract of ginger rhizome by normal phase HPLC. A low purity degree (calculated by the percentage of peak area) for both, [8]-gingerol (86%) and [10]-gingerol (84%) was achieved, while for the [6]-gingerol the purity was 99%. The purity degree obtained for each gingerol does not represent the real one, because HPLC system using UV detection does not guarantee the absence of other components in the sample.…”

“…4A and B). For [10]-gingerol, a concentration of 100 M was significantly effective in inhibiting MDA-MB-231 cell proliferation at 24 h of incubation in a rate of 75%, compared to cells seeded on normal medium (+FBS). The same pattern was observed after 48 h of [10]-gingerol incubation; there was a cell proliferation inhibition of about 90% (Fig.…”

“…HF were used in order to compare the effects of both [6]-, [8]and [10]-gingerol in a non tumor cell line (Figs. 4A and B and 5).…”

“…Together with [6]-gingerol, [8]-and [10]gingerol are the major pungent constituents in the ginger oleoresin from fresh rhizome, being [6]-gingerol the most abundant. Gingerols comprise a series of homologue substances differentiated by the length of their alkyl chains with [6]-, [8]-and [10]-gingerol having 10, 12 and 14 carbons in their unbranched alkyl chains, respectively [3].…”

“…Tumor cells are found to adopt multiple mechanisms to resist drugs, such as decreased uptake, and/or enhanced efflux and altered drug metabolism. Alteration in drug targets, activation of detoxification systems, enhanced DNA repair ability, and inhibition of apoptosis are also cancer cell strategies to resist against chemotherapy drugs [10].…”