Phospho-sulindac (OXT-922) inhibits the growth of human colon cancer cell lines: a redox/polyamine-dependent effect.

@article{Huang2010PhosphosulindacI,
  title={Phospho-sulindac (OXT-922) inhibits the growth of human colon cancer cell lines: a redox/polyamine-dependent effect.},
  author={Liqun Huang and Cai-hua Zhu and Yu Sun and Gang Xie and Gerardo G. Mackenzie and George Qiao and Despina Komninou and Basil Rigas},
  journal={Carcinogenesis},
  year={2010},
  volume={31 11},
  pages={
          1982-90
        }
}
Non-steroidal anti-inflammatory drugs such as sulindac are promising chemoprevention agents against colon cancer, but their weak potency and side effects limit their use for both chemoprevention and chemotherapy. Here, we evaluated the effect of a new sulindac derivative, phospho-sulindac or OXT-922, on the growth of human cancer cell lines and its mechanism of action. OXT-922 inhibited the growth of human cancer cell lines originating from colon, pancreas and breast ~11- to 30-fold more… 

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References

SHOWING 1-10 OF 48 REFERENCES
Phosphoaspirin (MDC-43), a novel benzyl ester of aspirin, inhibits the growth of human cancer cell lines more potently than aspirin: a redox-dependent effect.
TLDR
The results, establishing P-ASA as a potent inhibitor of the growth of several human cancer cell lines, suggest that it may possess broad anticancer properties, which merits further evaluation.
Sulindac sulfide, an aspirin-like compound, inhibits proliferation, causes cell cycle quiescence, and induces apoptosis in HT-29 colon adenocarcinoma cells.
TLDR
Results indicate that inhibition of cell cycle progression and induction of apoptotic cell death contribute to the anti-proliferative effects of sulindac and sulindAC sulfide in HT-29 cells.
Combined Effects of Sulindac and Suberoylanilide Hydroxamic Acid on Apoptosis Induction in Human Lung Cancer Cells
TLDR
It is demonstrated that at the suboptimal dose of 250 μM, sulindac significantly enhances SAHA-induced growth suppression and apoptosis of A549 human non-small cell lung cancer cells, primarily via enhanced collapse of the mitochondrial membrane potential, release of cytochrome c, and caspase activation.
A Novel Sulindac Derivative That Does Not Inhibit Cyclooxygenases but Potently Inhibits Colon Tumor Cell Growth and Induces Apoptosis with Antitumor Activity
TLDR
Results indicate that SSA has potential safety and efficacy advantages for colon cancer chemoprevention as well as utility for treating malignant disease if combined with chemotherapy.
Sulindac Enhances the Killing of Cancer Cells Exposed to Oxidative Stress
TLDR
Pretreatment of human colon and lung cancer cells with sulindac enhances killing by an oxidizing agent such as tert-butyl hydroperoxide (TBHP) or hydrogen peroxide, indicating that normal and cancer cells handle oxidative stress in different ways and sulindAC can enhance this difference.
Sulindac Enhances the Proteasome Inhibitor Bortezomib-Mediated Oxidative Stress and Anticancer Activity
TLDR
Sulindac synergistically augments the anticancer effects of bortezomib primarily through cooperative ROS generation and oxidative DNA damage, thereby representing a novel combination therapy against colon cancer.
The thioredoxin system mediates redox-induced cell death in human colon cancer cells: implications for the mechanism of action of anticancer agents.
TLDR
These findings indicate that the Trx system mediates to a large extent redox-induced cell death in response to anticancer agents and deserves further assessment as a candidate mechanism for the pharmacologic control of cancer.
Cyclooxygenase-independent Induction of Apoptosis by Sulindac Sulfone Is Mediated by Polyamines in Colon Cancer*
TLDR
Data suggest that apoptosis induced by sulindac sulfone is mediated, in part, by the COX-independent, PPAR-dependent transcriptional activation of SSAT, leading to reduced tissue polyamine contents in human colon cancer cells.
NO-donating aspirin inhibits the activation of NF-kappaB in human cancer cell lines and Min mice.
TLDR
Inhibition of NF-kappaB activation by NO-ASA may account for its chemopreventive efficacy, and an inhibitory mechanism different from suppressed subunit translocation into the nucleus is revealed.
...
...