Evidence map›Paper›PMID 25064160›Full record

ArticleToxicology and applied pharmacology2014

Hydroxychavicol, a betel leaf component, inhibits prostate cancer through ROS-driven DNA damage and apoptosis.

Sushma Reddy Gundala, Chunhua Yang, Rao Mukkavilli, Rutugandha Paranjpe, Meera Brahmbhatt, Vaishali Pannu, Alice Cheng, Michelle D Reid, Ritu Aneja

Open access · greenAbstract read
In one paragraph

Article in Toxicology and applied pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 90 citations in OpenAlex.

  1. Article
  2. Effects ofAnimals : an open access journal from MDPI · 2026
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  3. Article
  4. Article
  5. Bioactive Constituents ofDrug design, development and therapy · 2026
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Effects ofPharmaceuticals (Basel, Switzerland) · 2023
    Article
  11. Review
  12. Review
  13. Review
  14. Article
  15. Hydroxychavicol, a polyphenol fromJournal of Zhejiang University. Science. B · 2021
    Article
  16. Anti-Tumor Activity ofAntioxidants (Basel, Switzerland) · 2020
    Review
  17. Article
  18. Article
  19. Article
  20. Formation and biological targets of botanical o-quinones.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2018
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Sushma Reddy GundalaDepartment of Biology, Georgia State University, Atlanta, GA 30303, USA.
Chunhua YangDepartment of Biology, Georgia State University, Atlanta, GA 30303, USA.
Rao MukkavilliAdvinus Therapeutics, Karnataka, India.
Rutugandha ParanjpeDepartment of Biology, Georgia State University, Atlanta, GA 30303, USA.
Meera BrahmbhattDepartment of Biology, Georgia State University, Atlanta, GA 30303, USA.
Vaishali PannuDepartment of Biology, Georgia State University, Atlanta, GA 30303, USA.
Alice ChengDepartment of Biology, Georgia State University, Atlanta, GA 30303, USA.
Michelle D ReidDepartment of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
Ritu AnejaDepartment of Biology, Georgia State University, Atlanta, GA 30303, USA. Electronic address: raneja@gsu.edu.
Georgia State University · USEmory University · US

Funding

Evaluation of HSET as a Novel Theranostic Target for Breast Cancer TherapyR01CA169127 · NCI · GEORGIA STATE UNIVERSITY · PI ANEJA, RITU · 2012 to 2016
$1.7M
Evaluation of antiangiogenic role of EM011, a novel tubulin-binding agentR00CA131489 · NCI · GEORGIA STATE UNIVERSITY · PI ANEJA, RITU · 2010 to 2012
$732k
NCI NIH HHS R00 CA131489NCI NIH HHS R00CA131489NCI NIH HHS R01 CA169127NCI NIH HHS R01CA169127
6 · The paper itself

Abstract

Dietary phytochemicals are excellent ROS-modulating agents and have been shown to effectively enhance ROS levels beyond toxic threshold in cancer cells to ensure their selective killing while leaving normal cells unscathed. Here we demonstrate that hydroxychavicol (HC), extracted and purified from Piper betel leaves, significantly inhibits growth and proliferation via ROS generation in human prostate cancer, PC-3 cells. HC perturbed cell-cycle kinetics and progression, reduced clonogenicity and mediated cytotoxicity by ROS-induced DNA damage leading to activation of several pro-apoptotic molecules. In addition, HC treatment elicited a novel autophagic response as evidenced by the appearance of acidic vesicular organelles and increased expression of autophagic markers, LC3-IIb and beclin-1. Interestingly, quenching of ROS with tiron, an antioxidant, offered significant protection against HC-induced inhibition of cell growth and down regulation of caspase-3, suggesting the crucial role of ROS in mediating cell death. The collapse of mitochondrial transmembrane potential by HC further revealed the link between ROS generation and induction of caspase-mediated apoptosis in PC-3 cells. Our data showed remarkable inhibition of prostate tumor xenografts by ~72% upon daily oral administration of 150mg/kg bw HC by quantitative tumor volume measurements and non-invasive real-time bioluminescent imaging. HC was well-tolerated at this dosing level without any observable toxicity. This is the first report to demonstrate the anti-prostate cancer efficacy of HC in vitro and in vivo, which is perhaps attributable to its selective prooxidant activity to eliminate cancer cells thus providing compelling grounds for future preclinical studies to validate its potential usefulness for prostate cancer management.

Indexed as

Piper betleAnimalsApoptosisCell Line, TumorDNA DamageDose-Response Relationship, DrugEugenolHumansMaleMiceMice, Inbred BALB CMice, Inbred C57BLMice, NudePlant LeavesProstatic NeoplasmsReactive Oxygen Species2-hydroxychavicolEugenolReactive Oxygen SpeciesApoptosisAutophagyDNA damageHydroxychavicolProstate cancerReactive oxygen species (ROS)

Identifiers

PMID25064160
PMCPMC4363134
OpenAlexW2048136906

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.