ArticleAging2022
PKC is an indispensable factor in promoting environmental toxin chromium-mediated transformation and drug resistance.
Article in Aging, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed, 2 citations in OpenAlex.
- Protein Kinase C Epsilon Overexpression Protects the Heart Against Doxorubicin-Induced Cardiotoxicity Via Activating SIRT1.Cardiovascular toxicology · 2025Article
- Carcinogenic Mechanisms of Hexavalent Chromium: From DNA Breaks to Chromosome Instability and Neoplastic Transformation.Current environmental health reports · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Hexavalent chromium [Cr(VI)] pollution is a serious environmental problem, due to not only its toxicity but also carcinogenesis. Although studies reveal several features of Cr(VI)-induced carcinogenesis, the underlying mechanisms of how Cr(VI) orchestrates multiple mitogenic pathways to promote tumor initiation and progression remain not fully understood. Src/Ras and other growth-related pathways are shown to be key players in Cr(VI)-initiated tumor prone actions. The role of protein kinase C (PKC, an important signal transducer) in Cr(VI)-mediated carcinogenesis has not been thoroughly investigated. In this study, using human bronchial/lung epithelial cells and keratinocytes, we demonstrate that PKC activity is increased by transient or chronic Cr(VI) exposure, which plays no role in the activation of Src/Ras signaling and ROS upregulation by this metal toxin. PKC in chronic Cr(VI)-treated cells stabilizes Bcl-2 to mitigate doxorubicin (an anti-cancer drug)-mediated apoptosis. After the suppression of this kinase by GO6976 (a PKC inhibitor), the cells chronically exposed to Cr(VI) partially regain the sensitivity to doxorubicin. However, when co-suppressed PKC and Ras, the chronic Cr(VI)-treated cells become fully responsive to doxorubicin and are unable to be transformed. Taken together, our study provides a new insight into the mechanisms, in which PKC is an indispensable player and cooperates with other mitogenic pathways to achieve Cr(VI)-induced carcinogenesis as well as to establish drug resistance. The data also suggest that active PKC can serve as a potential biomarker for early detection of health damages by Cr(VI) and therapeutic target for developing new treatments for diseases caused by Cr(VI).
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.