| Reference | 1. Biochem Biophys Res Commun. 2015 Sep 11;465(1):137-44. doi:
10.1016/j.bbrc.2015.07.147. Epub 2015 Jul 30.
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The anti-esophageal cancer cell activity by a novel tyrosine/phosphoinositide
kinase inhibitor PP121.
<br>
Peng Y(1), Zhou Y(1), Cheng L(2), Hu D(3), Zhou X(3), Wang Z(3), Xie C(4), Zhou
F(5).
<br>
Author information: <br>
(1)Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor
Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan 430071, China;
Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan 430071, China.
(2)Department of Interventional Radiology, the Second Affiliated Hospital of
Soochow University, Soochow University, Suzhou 215001, China.
(3)Department of Radiation Oncology, Hubei Cancer Hospital, Wuhan 430071, China.
(4)Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor
Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Electronic address: [email protected].
(5)Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor
Biological Behaviors, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Electronic address: [email protected].
<br>
Here we explored the potential effect of PP121, a novel dual inhibitor of
tyrosine and phosphoinositide kinases, against human esophageal cancer cells. We
showed that PP121 exerted potent cytotoxic effect in primary (patient-derived)
and established (Eca-109, TE-1 and TE-3 lines) esophageal cancer cells, possibly
through activating caspase-3-dependnent apoptosis. PP121 was, however,
non-cytotoxic to the normal human esophageal epithelial cells (EECs). At the
molecular level, we showed that PP121 blocked Akt-mTOR (mammalian target of
rapamycin) activation in esophageal cancer cells, which was restored by
introducing a constitutively-active Akt (CA-Akt). Yet, CA-Akt only partly
inhibited cytotoxicity by PP121 in Eca-109 cells. Importantly, we showed that
PP121 inhibited nuclear factor kappa B (NFκB) signaling activation in esophageal
cancer cells, which appeared independent of Akt-mTOR blockage. In vivo, oral
administration of PP121 remarkably inhibited Eca-109 xenograft growth in nude
mice, and significantly improved mice survival. Further, the immunohistochemistry
(IHC) and Western blot assays analyzing xenografted tumors showed that PP121
inhibited Akt-mTOR and NFκB activations in vivo. Together, we demonstrate that
PP121 potently inhibits esophageal cancer cells in vitro and in vivo, possibly
through concurrently inhibiting Akt-mTOR and NFκB signalings.
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2. Tumour Biol. 2014 Sep;35(9):8659-64. doi: 10.1007/s13277-014-2118-3. Epub 2014
May 28.
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PP121, a dual inhibitor of tyrosine and phosphoinositide kinases, inhibits
anaplastic thyroid carcinoma cell proliferation and migration.
<br>
Che HY(1), Guo HY, Si XW, You QY, Lou WY.
<br>
Author information: <br>
(1)Shaoxing People/’s Hospital, Shaoxing Hospital of Zhejiang University, 568
Zhongxing North Road, Shaoxing, Zhejiang, 312000, People/’s Republic of China.
<br>
The tyrosine and phosphoinositide kinases play crucial roles in the regulation of
many cancer cell processes including cell survival and cell motility. Anaplastic
thyroid carcinoma (ATC) is a rare and deadly type of thyroid cancer, and so far,
there are no effective therapeutic compounds for ATC. Herein, we investigate the
anticancer activities of PP121, a dual inhibitor of tyrosine and phosphoinositide
kinases, in ATC therapy. We found that PP121 is effective at suppressing cell
viability, inducing cell apoptosis, and inhibiting cell migration and invasion.
The potential anticancer mechanism for PP121 might be its inhibitory effects on
phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways in ATC cells.
Furthermore, PP121 is effective at suppressing ATC tumor growth in vivo. In
summary, our studies suggest that PP121 might be a promising therapeutic compound
for ATC treatment, which might shed new light on ATC therapy.
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