Selective and Irreversible Induction of Necroptotic Cell Death in Lung Tumorspheres by Short-Term Exposure to Verapamil in Combination with Sorafenib.
Identifieur interne : 000C96 ( Main/Exploration ); précédent : 000C95; suivant : 000C97Selective and Irreversible Induction of Necroptotic Cell Death in Lung Tumorspheres by Short-Term Exposure to Verapamil in Combination with Sorafenib.
Auteurs : Juan Sebastian Yakisich [États-Unis] ; Yogesh Kulkarni [États-Unis] ; Neelam Azad [États-Unis] ; Anand Krishnan V. Iyer [États-Unis]Source :
- Stem cells international [ 1687-966X ] ; 2017.
Abstract
The presence of highly resistant cancer cells and the toxicity to normal cells are key factors that limit chemotherapy. Here, we used two models of highly resistant lung cancer cells: (1) adherent cells growing under prolonged periods of serum starvation (PPSS) and (2) cells growing as floating tumorspheres (FTs) to evaluate the effect of Verapamil (VP) in combination with Sorafenib (SF). Compared to cells growing under routine culture conditions (RCCs), PPPS cells or FTs were highly sensitive to short-term exposure (24 h) to VP 100 μM + SF 5 μM (VP100 + SF5). Recovery experiments exposing cells to VP100 + SF5 for 24 h followed by incubation in drug-free media for 48 h demonstrated that while PPSS as well as FT cells were unable to recover, cancer cells and the noncancerous cell line Beas-2B growing under RCCs were less sensitive and were also able to recover significantly. VP100 + SF5 induced significant changes in the expression of protein associated with apoptosis, autophagy, and to a lesser extent necroptosis. Coincubation experiments with z-VAD-FMK, necrostatin 1, or chloroquine showed evidence that necroptosis played a central role. Our data demonstrates that highly resistant cancer cells can be selectively eliminated by VP + SF and that necroptosis plays a central role.
DOI: 10.1155/2017/5987015
PubMed: 29201061
Affiliations:
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Iyer</name><affiliation wicri:level="2"><nlm:affiliation>School of Pharmacy, Department of Pharmaceutical Sciences, Hampton University, Hampton, VA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>School of Pharmacy, Department of Pharmaceutical Sciences, Hampton University, Hampton, VA</wicri:regionArea><placeName><region type="state">Virginie</region></placeName></affiliation></author></analytic><series><title level="j">Stem cells international</title><idno type="ISSN">1687-966X</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The presence of highly resistant cancer cells and the toxicity to normal cells are key factors that limit chemotherapy. Here, we used two models of highly resistant lung cancer cells: (1) adherent cells growing under prolonged periods of serum starvation (PPSS) and (2) cells growing as floating tumorspheres (FTs) to evaluate the effect of Verapamil (VP) in combination with Sorafenib (SF). Compared to cells growing under routine culture conditions (RCCs), PPPS cells or FTs were highly sensitive to short-term exposure (24 h) to VP 100 <i>μ</i>M + SF 5 <i>μ</i>M (VP100 + SF5). Recovery experiments exposing cells to VP100 + SF5 for 24 h followed by incubation in drug-free media for 48 h demonstrated that while PPSS as well as FT cells were unable to recover, cancer cells and the noncancerous cell line Beas-2B growing under RCCs were less sensitive and were also able to recover significantly. VP100 + SF5 induced significant changes in the expression of protein associated with apoptosis, autophagy, and to a lesser extent necroptosis. Coincubation experiments with z-VAD-FMK, necrostatin 1, or chloroquine showed evidence that necroptosis played a central role. Our data demonstrates that highly resistant cancer cells can be selectively eliminated by VP + SF and that necroptosis plays a central role.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Virginie</li></region></list><tree><country name="États-Unis"><region name="Virginie"><name sortKey="Yakisich, Juan Sebastian" sort="Yakisich, Juan Sebastian" uniqKey="Yakisich J" first="Juan Sebastian" last="Yakisich">Juan Sebastian Yakisich</name></region><name sortKey="Azad, Neelam" sort="Azad, Neelam" uniqKey="Azad N" first="Neelam" last="Azad">Neelam Azad</name><name sortKey="Iyer, Anand Krishnan V" sort="Iyer, Anand Krishnan V" uniqKey="Iyer A" first="Anand Krishnan V" last="Iyer">Anand Krishnan V. Iyer</name><name sortKey="Kulkarni, Yogesh" sort="Kulkarni, Yogesh" uniqKey="Kulkarni Y" first="Yogesh" last="Kulkarni">Yogesh Kulkarni</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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