Modulating Polo-Like Kinase 1 as a Means for Cancer Chemoprevention

Schmit, Travis L.; Ledesma, Mark C.; Ahmad, Nihal

doi:10.1007/s11095-010-0051-8

Cited by 28 publications

(24 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…43 Nevertheless, Plk1 activity slowly rises from S through G2 and peaks in mitosis. Plk1 not only mediates centriole maturation 42,44,45 but also primes centrioles for disengagement 34 by phosphorylating cohesin and accelerating its cleavage by separase. 46 In addition, Plk1 may regulate centrosomal localization of shugoshin and mediate centriole disengagement by modifying shugoshin's activity in preserving centriole cohesion.…”

Section: Excess Baggage: How Cancer Cells Acquire Extra Centrosomesmentioning

confidence: 99%

Let's huddle to prevent a muddle: centrosome declustering as an attractive anticancer strategy

2012

View full text Add to dashboard Cite

Nearly a century ago, cell biologists postulated that the chromosomal aberrations blighting cancer cells might be caused by a mysterious organelle-the centrosome-that had only just been discovered. For years, however, this enigmatic structure was neglected in oncologic investigations and has only recently reemerged as a key suspect in tumorigenesis. A majority of cancer cells, unlike healthy cells, possess an amplified centrosome complement, which they manage to coalesce neatly at two spindle poles during mitosis. This clustering mechanism permits the cell to form a pseudo-bipolar mitotic spindle for segregation of sister chromatids. On rare occasions this mechanism fails, resulting in declustered centrosomes and the assembly of a multipolar spindle. Spindle multipolarity consigns the cell to an almost certain fate of mitotic arrest or death. The catastrophic nature of multipolarity has attracted efforts to develop drugs that can induce declustering in cancer cells. Such chemotherapeutics would theoretically spare healthy cells, whose normal centrosome complement should preclude multipolar spindle formation. In search of the 'Holy Grail' of nontoxic, cancer cell-selective, and superiorly efficacious chemotherapy, research is underway to elucidate the underpinnings of centrosome clustering mechanisms. Here, we detail the progress made towards that end, highlighting seminal work and suggesting directions for future research, aimed at demystifying this riddling cellular tactic and exploiting it for chemotherapeutic purposes. We also propose a model to highlight the integral role of microtubule dynamicity and the delicate balance of forces on which cancer cells rely for effective centrosome clustering. Finally, we provide insights regarding how perturbation of this balance may pave an inroad for inducing lethal centrosome dispersal and death selectively in cancer cells.

show abstract

Section: Excess Baggage: How Cancer Cells Acquire Extra Centrosomesmentioning

confidence: 99%

Let's huddle to prevent a muddle: centrosome declustering as an attractive anticancer strategy

2012

View full text Add to dashboard Cite

show abstract

“…In recent years, some of these reviews touched the general overview for the bioactive aspect for phytochemical compounds [3-12], or specific compounds such as Vitamin E from plant oil [13-15], boron-rich natural compound [16], hydroxytyrosol from virgin olive oil [17], resveratrol from grapes [18], phytoestrogens most notably from soybean [19, 20], or EGCG from green tea polyphenols [21], while the others are more specific for certain cancers, e.g., colorectal cancer [22, 23], breast cancer [14, 24], head and neck cancer [25], pancreatic cancer [26], prostate cancer [27], or protein targets and pathway mechanisms, such as Nrf2 [28], COX-2 [29], PLK1 [30], angiogenesis [31]. In this review, we will provide a comprehensive summary for the current status of the research and challenges in this area [32].…”

Section: Introductionmentioning

confidence: 99%

Plants vs. Cancer: A Review on Natural Phytochemicals in Preventing and Treating Cancers and Their Druggability

Wang

Khor²,

Shu³

et al. 2012

ACAMC

478

288

View full text Add to dashboard Cite

Cancer remains to be one of the leading causes of death in the United States and around the world. The advent of modern drug-targeted therapies has undeniably improved cancer patients’ cares. However, advanced metastasized cancer remains untreatable. Hence, continued searching for a safer and more effective chemoprevention and treatment is clearly needed for the improvement of the efficiency and to lower the treatment cost for cancer care. Cancer chemoprevention with natural phytochemical compounds is an emerging strategy to prevent, impede, delay, or cure cancer. This review summarizes the latest research in cancer chemoprevention and treatment using the bioactive components from natural plants. Relevant molecular mechanisms involved in the pharmacological effects of these phytochemicals are discussed. Pharmaceutical developmental challenges and opportunities in bringing the phytochemicals into the market are also explored. The authors wish to expand this research area not only for their scientific soundness, but also for their potential druggability.

show abstract

“…PLK1 also plays a key role in chromosome segregation, cytokinesis, and mitosis exit through phosphorylation and degradation of the anaphase promoter complex and its inhibitor. 6 Altered PLK1 expression has been described in different neoplasias and correlated with prognosis. 7 The inhibition of this kinase by different methods has been shown to cause cell cycle arrest and to increase apoptosis in several models.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

Pezuk

Brassesco

Morales

et al. 2013

Cancer Biotherapy and Radiopharmaceuticals

View full text Add to dashboard Cite

Despite efforts to improve surgical, radiologic, and chemotherapeutic strategies, the outcome of patients with glioblastoma (GBM) is still poor. Polo-like kinase 1 (PLK1) is a serine/threonine kinase that plays key roles in cell cycle control and has been associated with tumor growth and prognosis. Here, we aimed at testing the radiosensitizing effects of the PLK1 inhibitor BI 2536 on eight GBM cell lines. For cell cycle analysis, T98G, U251, U343 MG-a, LN319, SF188, U138 MG, and U87 MG cell lines were treated with 10, 50, or 100 nM of BI 2536 for 24 hours. In addition, cell cultures exposed to BI 2536 50 nM for 24 hours were irradiated with c-rays from 60 Cobalt source at final doses of 2, 4, and 6 Gy. Combinatorial effects were evaluated through proliferation and clonogenic capacity assays. Treatment with BI 2536 caused mitotic arrest after 24 hours, and increased apoptosis in GBM cells. Moreover, our results demonstrate that pretreatment with this drug sensitized six out of seven GBM cell lines to different doses of c-irradiation as shown by decreased growth and abrogation of colony-formation capacity. Our data suggest that PLK1 blockage has a radiosensitizing effect on GBM, which could improve treatment strategies for this devastating tumor.

show abstract

Modulating Polo-Like Kinase 1 as a Means for Cancer Chemoprevention

Cited by 28 publications

References 90 publications

Let's huddle to prevent a muddle: centrosome declustering as an attractive anticancer strategy

Let's huddle to prevent a muddle: centrosome declustering as an attractive anticancer strategy

Plants vs. Cancer: A Review on Natural Phytochemicals in Preventing and Treating Cancers and Their Druggability

Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

Contact Info

Product

Resources

About