The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Piperine, an alkaloid from black pepper, inhibits growth of human colon cancer cells via G1 arrest and apoptosis triggered by endoplasmic reticulum stress
Abstract
Piperine, a piperidine alkaloid present in black pepper, inhibits the growth of cancer cells, although the mechanism of action is not well understood. In this study, we show that piperine (75–150 µM) inhibited the growth of several colon cancer cell lines but had little effect on the growth of normal fibroblasts and epithelial cells. Piperine inhibited HT‐29 colon carcinoma cell proliferation by causing G1 phase cell cycle arrest that was associated with decreased expression of cyclins D1 and D3 and their activating partner cyclin‐dependent kinases 4 and 6, as well as reduced phosphorylation of the retinoblastoma protein and up‐regulation of p21/WAF1 and p27/KIP1 expression. In addition, piperine caused hydroxyl radical production and apoptosis that was partially dependent on the production of reactive oxygen species. Piperine‐treated HT‐29 cells showed loss of mitochondrial membrane integrity and cleavage of poly (ADP‐ribose) polymerase‐1, as well as caspase activation and reduced apoptosis in the presence of the pan‐caspase inhibitor zVAD‐FMK. Increased expression of the endoplasmic reticulum stress‐associated proteins inositol‐requiring 1α protein, C/EBP homologous protein, and binding immunoglobulin protein, and activation of c‐Jun N‐terminal kinase and p38 mitogen‐activated protein kinase, as well as decreased phosphorylation of Akt and reduced survivin expression were also observed in piperine‐treated HT‐29 cells. Furthermore, piperine inhibited colony formation by HT‐29 cells, as well as the growth of HT‐29 spheroids. Cell cycle arrest and endoplasmic reticulum stress‐associated apoptosis following piperine treatment of HT‐29 cells provides the first evidence that piperine may be useful in the treatment of colon cancer. © 2014 Wiley Periodicals, Inc.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Requirement for p53 and p21 to Sustain G 2 Arrest After DNA Damage
Bunz, F., Dutriaux, A., Lengauer, C., Waldman, T., Zhou, S., Brown, J. P., Sedivy, J. M., Kinzler, K. W., & Vogelstein, B. (1998) · Science · doi:10.1126/science.282.5393.1497 · Cited by 2,803
SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase
Bennett, B. L., Sasaki, D. T., Murray, B. W., O'Leary, E. C., Sakata, S. T., Xu, W., Leisten, J. C., Motiwala, A., Pierce, S., Satoh, Y., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.251194298 · Cited by 2,558 · cited 3×
“The pan-caspase inhibitor zVAD-FMK, the c-Jun N-terminal kinase (JNK) inhibitor SP600125, and the p38mitogen-activated protein kinase (MAPK) inhibitor SB203580 were purchased from EMD Biosciences (San Diego, CA).”
BackgroundGlycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellular localization
Diehl, J. A., Cheng, M., Roussel, M. F., & Sherr, C. J. (1998) · Genes & Development · doi:10.1101/gad.12.22.3499 · Cited by 2,130
Mitochondrial dynamics and apoptosis
Suen, D.-F., Norris, K. L., & Youle, R. J. (2008) · Genes & Development · doi:10.1101/gad.1658508 · Cited by 1,270 · cited 1×
“Western blot analysis of lysates from piperine-treated HT-29 cells showed an increase in cytochrome c release from mitochondria, indicating loss of mitochondrial membrane integrity that is often associated with apoptosis induction [34] (Figure 5B).”
BackgroundTRB3: A tribbles Homolog That Inhibits Akt/PKB Activation by Insulin in Liver
Du, K., Herzig, S., Kulkarni, R. N., & Montminy, M. (2003) · Science · doi:10.1126/science.1079817 · Cited by 842
Luca, A. C., Mersch, S., Deenen, R., Schmidt, S., Messner, I., Schäfer, K.-L., Baldus, S. E., Huckenbeck, W., Piekorz, R. P., Knoefel, W. T., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059689 · Cited by 341
Volak, L. P., Ghirmai, S., Cashman, J. R., & Court, M. H. (2008) · Drug Metabolism and Disposition · doi:10.1124/dmd.108.020552 · Cited by 214
Platel, K., & Srinivasan, K. (1996) · International Journal of Food Sciences and Nutrition · doi:10.3109/09637489609028561 · Cited by 209
Cancer cell signaling pathways targeted by spice-derived nutraceuticals
Sung, B., Prasad, S., Yadav, V. R., & Aggarwal, B. B. (2012) · Nutrition and Cancer · doi:10.1080/01635581.2012.630551 · Cited by 204
Cited by
Kim, C., & Kim, B. (2018) · Nutrients · doi:10.3390/nu10081021 · Cited by 493
Natural products: A lead for drug discovery and development
Chopra, B., & Dhingra, A. K. (2021) · Phytotherapy Research · doi:10.1002/ptr.7099 · Cited by 469
Piperine: A review of its biological effects
Haq, I., Imran, M., Nadeem, M., Tufail, T., Gondal, T. A., & Mubarak, M. S. (2021) · Phytotherapy Research · doi:10.1002/ptr.6855 · Cited by 434
Targeting arachidonic acid pathway by natural products for cancer prevention and therapy
Yarla, N. S., Bishayee, A., Sethi, G., Reddanna, P., Kalle, A. M., Dhananjaya, B. L., Dowluru, K. S. V. G. K., Chintala, R., & Duddukuri, G. R. (2016) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2016.02.001 · Cited by 364
Spices for Prevention and Treatment of Cancers
Zheng, J., Zhou, Y., Li, Y., Xu, D.-P., Li, S., & Li, H.-B. (2016) · Nutrients · doi:10.3390/nu8080495 · Cited by 329
Current and emerging therapeutic approaches for colorectal cancer: A comprehensive review
Kumar, A., Gautam, V., Sandhu, A., Rawat, K., Sharma, A., & Saha, L. (2023) · World Journal of Gastrointestinal Surgery · doi:10.4240/wjgs.v15.i4.495 · Cited by 272
Herbs that heal: Nature’s pharmacy endowed remedies for better health
Mehrotra, N. (2021) · Annals of Phytomedicine: An International Journal · doi:10.21276/ap.2021.10.1.2 · Cited by 27
Matsunaga, T., Reisenman, C. E., Goldman-Huertas, B., Rajshekar, S., Suzuki, H. C., Tadres, D., Wong, J., Louis, M., Ramírez, S. R., & Whiteman, N. K. (2025) · Molecular Biology and Evolution · doi:10.1093/molbev/msaf164 · Cited by 9
Metadata
- Authors
- Yaffe, P. B., Power Coombs, M. R., Doucette, C. D., Walsh, M., & Hoskin, D. W.
- Venue
- Molecular Carcinogenesis
- Publisher
- Wiley
- Published
- 2014-05-13
- Volume
- 54
- Issue
- 10
- Pages
- 1070-1085
- ISSN
- 0899-1987 (ISSN-L)
- 1098-2744
- OpenAlex
- W2157011225
- Cited by
- 188
- References
- 9
- FWCI
- 8.06
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.