Inhibition of Polo-like Kinase 1 (Plk1) Enhances the Antineoplastic Activity of Metformin in Prostate Cancer

Shao, Chun-Kui; Ahmad, Nihal; Hodges, Kurt; Kuang, Shihuan; Ratliff, Tim; Liu, Xiaoqi

doi:10.1074/jbc.m114.596817

Cited by 38 publications

(32 citation statements)

References 48 publications

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“…Recently, it was shown that the low expression of Polo-like kinase 1 in RWPE-1 cells could explain this resistance to metformin (Shao et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

The effects of metformin and simvastatin on the growth of LNCaP and RWPE-1 prostate epithelial cell lines

Pennanen

Syvälä

Bläuer

et al. 2016

European Journal of Pharmacology

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“…Recently, it was shown that the low expression of Polo-like kinase 1 in RWPE-1 cells could explain this resistance to metformin (Shao et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

The effects of metformin and simvastatin on the growth of LNCaP and RWPE-1 prostate epithelial cell lines

Pennanen

Syvälä

Bläuer

et al. 2016

European Journal of Pharmacology

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“…Recently, Plk1 inhibition was shown to enhance the antineoplastic activity of metformin in prostate cancer (52). Cancer cells maintain tumor growth through increased glycolysis (Warburg effect) and glutaminolysis (glutamine addition) to satisfy the energy and carbon backbone needs, respectively (53).…”

Section: Plk1 In Therapy Resistancementioning

confidence: 99%

“…It is encouraging to note that metformin was found to inhibit the development of CRPC in a clinical trial with 3000 patients (57). Interestingly, inhibition of Plk1 enhances the antineoplastic activity of metformin in prostate cancer through both p53 and metabolic pathways (Figure 2F) (52). This gives us a hope that Plk1 inhibitors could enhance the anticancer activities of metformin or other metabolism and growth-regulating agents to the point that they could be clinically useful in cancer management.…”

Section: Plk1 In Therapy Resistancementioning

confidence: 99%

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Plk1 Inhibitors in Cancer Therapy: From Laboratory to Clinics

Gutteridge

Ndiaye

Liu

et al. 2016

Molecular Cancer Therapeutics

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342

272

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Polo-like kinase 1 (Plk1) overexpression has been shown to occur in a wide range of tumors, prompting research and development of Plk1 inhibitors as a means of cancer treatment. This review discusses recent advances in the development of Plk1 inhibitors for cancer management. Plk1 inhibition has been shown to cause mitotic block and apoptosis of cells with higher mitotic index and therefore higher Plk1 expression. The potential of Plk1 inhibitors as cancer therapeutics has been widely investigated. However, a complete understanding of Plk1 biology/mechanism is yet to be fully achieved. Resistance to certain chemotherapeutic drugs has been linked to Plk1 overexpression, and Plk1-mediated mitotic events such as microtubule rearrangement have been found to reduce the efficacy of chemotherapeutic agents. The Plk1 inhibitor, volasertib, has shown considerable promise in clinical studies, having reached phase III trials. However, preclinical success with Plk1 inhibitors has not translated well into clinical success. In our view, combined therapies targeting other relevant pathways together with Plk1 may be vital to combat issues observed with monotherapy, especially resistance. In addition, research should also be directed towards understanding the mechanisms of Plk1 and designing additional next generations of specific, potent Plk1 inhibitors to target cancer.

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“…Another interesting issue of therapeutic relevance is that Plk-1 inhibition has been reported to enhance both radiation and anticancer drug efficacy in many tumor types (87)(88)(89)(90)(91)(92). Moreover, Plk1 overexpression has been shown to be critical for PTEN-depleted cells to adapt to mitotic stress, thereby facilitating the loss of PTEN-induced PCa formation (93), and its inhibition has been described to enhance the anticancer activity of metformin (94).…”

Section: The Wnt/␤-catenin Pathway In Prostate Cancermentioning

confidence: 99%

Cross Talk between Wnt/β-Catenin and CIP2A/Plk1 Signaling in Prostate Cancer: Promising Therapeutic Implications

Cristóbal

Rojo

Madoz‐Gúrpide

et al. 2016

Molecular and Cellular Biology

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Aberrant activation of the Wnt/␤-catenin pathway and polo-like kinase 1 (Plk1) overexpression represent two common events in prostate cancer with relevant functional implications. This minireview analyzes their potential therapeutic significance in prostate cancer based on their role as androgen receptor (AR) signaling regulators and the pivotal role of the tumor suppressor protein phosphatase 2A (PP2A) modulating these pathways.

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Inhibition of Polo-like Kinase 1 (Plk1) Enhances the Antineoplastic Activity of Metformin in Prostate Cancer

Cited by 38 publications

References 48 publications

The effects of metformin and simvastatin on the growth of LNCaP and RWPE-1 prostate epithelial cell lines

The effects of metformin and simvastatin on the growth of LNCaP and RWPE-1 prostate epithelial cell lines

Plk1 Inhibitors in Cancer Therapy: From Laboratory to Clinics

Cross Talk between Wnt/β-Catenin and CIP2A/Plk1 Signaling in Prostate Cancer: Promising Therapeutic Implications

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