Novel PKC-ζ to p47phox interaction is necessary for transformation from blebbishields

Goodwin G. Jinesh; Rikiya Taoka; Qiang Zhang; Siddharth Gorantla; Ashish M. Kamat

doi:10.1038/srep23965

Novel PKC-ζ to p47^phox interaction is necessary for transformation from blebbishields

Goodwin G. Jinesh, Rikiya Taoka, Qiang Zhang, Siddharth Gorantla, Ashish M. Kamat

Urology

Research output: Contribution to journal › Article › peer-review

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Abstract

Cancer stem cells are capable of transformation after apoptosis through the blebbishield emergency program. Reactive oxygen species (ROS) play an essential role in transformation. Understanding how ROS are linked to blebbishield-mediated transformation is necessary to develop efficient therapeutics that target the resurrection of cancer stem cells. Here we demonstrate that a novel PKC-ζ to p47^phox interaction is required for ROS production in cancer cells. The combined use of the S6K inhibitor BI-D1870 with TNF-α inhibited the PKC-ζ to p47^phox interaction, inhibited ROS production, degraded PKC-ζ, and activated caspases-3 and -8 to block transformation from blebbishields. BI-D1870 also inhibited transformation from cycloheximide-generated blebbishields. Thus ROS and the PKC-ζ to p47^phox interaction are valid therapeutic targets to block transformation from blebbishields.

Original language	English (US)
Article number	23965
Journal	Scientific reports
Volume	6
DOIs	https://doi.org/10.1038/srep23965
State	Published - Apr 4 2016

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abstract = "Cancer stem cells are capable of transformation after apoptosis through the blebbishield emergency program. Reactive oxygen species (ROS) play an essential role in transformation. Understanding how ROS are linked to blebbishield-mediated transformation is necessary to develop efficient therapeutics that target the resurrection of cancer stem cells. Here we demonstrate that a novel PKC-ζ to p47phox interaction is required for ROS production in cancer cells. The combined use of the S6K inhibitor BI-D1870 with TNF-α inhibited the PKC-ζ to p47phox interaction, inhibited ROS production, degraded PKC-ζ, and activated caspases-3 and -8 to block transformation from blebbishields. BI-D1870 also inhibited transformation from cycloheximide-generated blebbishields. Thus ROS and the PKC-ζ to p47phox interaction are valid therapeutic targets to block transformation from blebbishields.",

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AU - Jinesh, Goodwin G.

AU - Taoka, Rikiya

AU - Zhang, Qiang

AU - Gorantla, Siddharth

AU - Kamat, Ashish M.

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N2 - Cancer stem cells are capable of transformation after apoptosis through the blebbishield emergency program. Reactive oxygen species (ROS) play an essential role in transformation. Understanding how ROS are linked to blebbishield-mediated transformation is necessary to develop efficient therapeutics that target the resurrection of cancer stem cells. Here we demonstrate that a novel PKC-ζ to p47phox interaction is required for ROS production in cancer cells. The combined use of the S6K inhibitor BI-D1870 with TNF-α inhibited the PKC-ζ to p47phox interaction, inhibited ROS production, degraded PKC-ζ, and activated caspases-3 and -8 to block transformation from blebbishields. BI-D1870 also inhibited transformation from cycloheximide-generated blebbishields. Thus ROS and the PKC-ζ to p47phox interaction are valid therapeutic targets to block transformation from blebbishields.

AB - Cancer stem cells are capable of transformation after apoptosis through the blebbishield emergency program. Reactive oxygen species (ROS) play an essential role in transformation. Understanding how ROS are linked to blebbishield-mediated transformation is necessary to develop efficient therapeutics that target the resurrection of cancer stem cells. Here we demonstrate that a novel PKC-ζ to p47phox interaction is required for ROS production in cancer cells. The combined use of the S6K inhibitor BI-D1870 with TNF-α inhibited the PKC-ζ to p47phox interaction, inhibited ROS production, degraded PKC-ζ, and activated caspases-3 and -8 to block transformation from blebbishields. BI-D1870 also inhibited transformation from cycloheximide-generated blebbishields. Thus ROS and the PKC-ζ to p47phox interaction are valid therapeutic targets to block transformation from blebbishields.

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Novel PKC-ζ to p47^phox interaction is necessary for transformation from blebbishields

Abstract

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