| Title |
Sanguinarine causes cell cycle blockade and apoptosis of human prostate carcinoma cells via modulation of cyclin kinase inhibitor-cyclin-cyclin-dependent kinase machinery
|
|---|---|
| Published in |
Molecular Cancer Therapeutics, August 2004
|
| DOI | 10.1158/1535-7163.933.3.8 |
| Pubmed ID | |
| Authors |
Vaqar Mustafa Adhami, Moammir Hasan Aziz, Shannon R. Reagan-Shaw, Minakshi Nihal, Hasan Mukhtar, Nihal Ahmad |
| Abstract |
Prostate cancer is the second leading cause of cancer-related deaths in males in the United States. This warrants the development of novel mechanism-based strategies for the prevention and/or treatment of prostate cancer. Several studies have shown that plant-derived alkaloids possess remarkable anticancer effects. Sanguinarine, an alkaloid derived from the bloodroot plant Sanguinaria canadensis, has been shown to possess antimicrobial, anti-inflammatory, and antioxidant properties. Previously, we have shown that sanguinarine possesses strong antiproliferative and proapoptotic properties against human epidermoid carcinoma A431 cells and immortalized human HaCaT keratinocytes. Here, employing androgen-responsive human prostate carcinoma LNCaP cells and androgen-unresponsive human prostate carcinoma DU145 cells, we studied the antiproliferative properties of sanguinarine against prostate cancer. Sanguinarine (0.1-2 micromol/L) treatment of LNCaP and DU145 cells for 24 hours resulted in dose-dependent (1) inhibition of cell growth [as evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay], (2) arrest of cells in G0-G1 phase of the cell cycle (as assessed by DNA cell cycle analysis), and (3) induction of apoptosis (as evaluated by DNA ladder formation and flow cytometry). To define the mechanism of antiproliferative effects of sanguinarine against prostate cancer, we studied the effect of sanguinarine on critical molecular events known to regulate the cell cycle and the apoptotic machinery. Immunoblot analysis showed that sanguinarine treatment of both LNCaP and DU145 cells resulted in significant (1) induction of cyclin kinase inhibitors p21/WAF1 and p27/KIP1; (2) down-regulation of cyclin E, D1, and D2; and (3) down-regulation of cyclin-dependent kinase 2, 4, and 6. A highlight of this study was the fact that sanguinarine induced growth inhibitory and antiproliferative effects in human prostate carcinoma cells irrespective of their androgen status. To our knowledge, this is the first study showing the involvement of cyclin kinase inhibitor-cyclin-cyclin-dependent kinase machinery during cell cycle arrest and apoptosis of prostate cancer cells by sanguinarine. These results suggest that sanguinarine may be developed as an agent for the management of prostate cancer. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 52 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 52 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 11 | 21% |
| Student > Bachelor | 8 | 15% |
| Researcher | 6 | 12% |
| Student > Master | 4 | 8% |
| Lecturer | 2 | 4% |
| Other | 5 | 10% |
| Unknown | 16 | 31% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 12 | 23% |
| Biochemistry, Genetics and Molecular Biology | 10 | 19% |
| Chemistry | 5 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 4% |
| Business, Management and Accounting | 1 | 2% |
| Other | 5 | 10% |
| Unknown | 17 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 14. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 22 March 2023.
All research outputs
#2,654,960
of 25,377,790 outputs
Outputs from Molecular Cancer Therapeutics
#317
of 4,065 outputs
Outputs of similar age
#3,828
of 60,684 outputs
Outputs of similar age from Molecular Cancer Therapeutics
#1
of 28 outputs
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So far Altmetric has tracked 4,065 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.8. This one has done particularly well, scoring higher than 92% of its peers.
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We're also able to compare this research output to 28 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 96% of its contemporaries.