Cancer Chemoprevention by Targeting Proteasomal Degradation

Yang, Chung S.; Chin, Khew‐Voon; Lambert, Joshua D.

doi:10.1158/1078-0432.ccr-04-0416

Cited by 6 publications

(2 citation statements)

References 10 publications

(7 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mutations in this pathway can cause pleiotropic defects because of its involvement in virtually all aspects of cell function. Consequently, the characterization of the Ub/proteasome system for the development of treatment for cancer and other malignancies is an area of active investigation (4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Increased Proteasome Activity, Ubiquitin-Conjugating Enzymes, and eEF1A Translation Factor Detected in Breast Cancer Tissue

2005

View full text Add to dashboard Cite

The ubiquitin (Ub)/proteasome pathway facilitates the degradation of damaged proteins and regulators of growth and stress response. The activation of this pathway in various cancers and malignancies has been described, and several genetic determinants of breast cancer, including BRCA1 and BRCA2, are linked to protein degradation. To investigate the involvement of the Ub/proteasome system in breast cancer, we examined a collection of 25 patient-matched breast cancer and normal adjacent tissues and detected activation of numerous components of the Ub/proteasome pathway. The activity of the proteasome, and levels of proteasome subunits and various targeting factors, were increased in >90% of primary breast cancer tissue specimens. In contrast, no activation was observed in benign solid tumors, indicating that the response is specific to abnormal growth in neoplastic cells. Additionally, the accumulation of high levels of certain Ub-conjugating enzymes (UbcH1, UbcH2, and UbcH5), was specific to breast cancer, as no change in abundance was detected in primary colon cancer tissue extracts. Surprisingly, the Ub/proteasome system was not activated in a wellcharacterized cell culture-based breast cancer model system. Collectively, these findings suggest that the analysis of primary breast cancer tissue samples will be indispensable for the biochemical characterization of neoplastic growth and for the development of therapeutics. (Cancer Res 2005; 65(13): 5599-606)

show abstract

Section: Introductionmentioning

confidence: 99%

Increased Proteasome Activity, Ubiquitin-Conjugating Enzymes, and eEF1A Translation Factor Detected in Breast Cancer Tissue

2005

View full text Add to dashboard Cite

show abstract

“…Cyclins activate cyclin-dependent kinases to promote cell growth, and their overexpression has been associated with tumor development [37]. Some chemopreventive agents are thought to inhibit the expression and activity of cyclins such as cyclin D1, A, B, as well as cyclin E/cyclin-dependent kinase 2 and cyclin B1/cyclin-dependent kinase 1 [38].…”

Section: Inhibition Of Cell Cycle Progressionmentioning

confidence: 99%

Molecular Basis of Traditional Chinese Medicine in Cancer Chemoprevention

Wang

Penchala²,

Prabhu³

et al. 2010

CDDT

View full text Add to dashboard Cite

Cancer is the second leading cause of death, for which current therapeutic approaches are still very limited. Chemoprevention is an important approach to decreasing cancer morbidity and mortality by the use of non-toxic natural or synthetic substances to reverse the processes of initiation and subsequent progression of cancer. A substantial amount of evidence from human, animal and cell line studies has shown that many herbal products used for traditional Chinese medicine (TCM) can exert chemopreventive effects. The underlying theory for TCM to treat or prevent cancer is to bring the patient back to a healthy state by modifying multiple cancer-causing events. Since carcinogenesis involves multiple abnormal genes/pathways, using TCM in cancer chemoprevention may be superior to the agents targeting a single molecular target alone. However, before TCM can be accepted universally as complementary and alternative medicine for cancer treatment and prevention, it is crucial to understand the molecular basis for their effects. This review highlights several known molecular mechanisms of selected TCM in chemoprevention. Many TCM products or single active components have been reported to inhibit a variety of processes in cancer cell growth, invasion and metastasis by modulating a wide range of molecular targets, including cyclooxygenase-2 (COX-2), nuclear factor-Kappa B (NF-kappaB) and nuclear factor erythroid 2 -related factor 2 (Nrf2)-mediated antioxidant signaling pathways. The TCM and their active components with potent chemopreventive effects can be considered as promising lead agents for the design of more effective and less toxic agents for cancer chemoprevention.

show abstract