TTK is a potential therapeutic target for cisplatin-resistant ovarian cancer

Liu, Yixuan; Zhü, Kèyù; Guan, Xiaolin; Xie, Shuanshuan; Wang, Yanchun; Tong, Ying; Guo, Lin; Zheng, Hui; Lu, Renquan

doi:10.1186/s13048-021-00884-z

Cited by 20 publications

(20 citation statements)

References 29 publications

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“…However, >10% apoptosis and dead A2780cis cells were observed even at 0 h (non-treated cell group). This effect could be due to cell death during experimental protocol, which has been previously reported ( 45 , 46 ). Therefore, additional assays on the apoptosis of non-treated (0 h) cells at 24, 48 and 72 h were performed to verify the effects of trans-(±)-kusunokinin on apoptosis at 72 h ( Fig.…”

Section: Discussionmentioning

confidence: 51%

Effects of trans‑(±)‑kusunokinin on chemosensitive and chemoresistant ovarian cancer cells

et al. 2021

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Ovarian cancer ranks eighth in cancer incidence and mortality among women worldwide. Cisplatin-based chemotherapy is commonly used for patients with ovarian cancer. However, the clinical efficacy of cisplatin is limited due to the occurrence of adverse side effects and development of cancer chemoresistance during treatment. Trans-(±)-kusunokinin has been previously reported to inhibit cell proliferation and induce cell apoptosis in various cancer cell types, including breast, colon and cholangiocarcinoma. However, the potential effects of (±)-kusunokinin on ovarian cancer remains unknown. In the present study, chemosensitive ovarian cancer cell line A2780 and chemoresistant ovarian cancer cell lines A2780cis, SKOV-3 and OVCAR-3 were treated with trans-(±)-kusunokinin to investigate its potential effects. MTT, colony formation, apoptosis and multi-caspase assays were used to determine cytotoxicity, the ability of single cells to form colonies, induction of apoptosis and multi-caspase activity, respectively. Moreover, western blot analysis was performed to determine the proteins level of topoisomerase II, cyclin D1, CDK1, Bax and p53-upregulated modulator of apoptosis (PUMA). The results demonstrated that trans-(±)-kusunokinin exhibited the strongest cytotoxicity against A2780cis cells with an IC 50 value of 3.4 µM whilst also reducing the colony formation of A2780 and A2780cis cells. Trans-(±)-kusunokinin also induced the cells to undergo apoptosis and increased multi-caspase activity in A2780 and A2780cis cells. This compound significantly downregulated topoisomerase II, cyclin D1 and CDK1 expression, but upregulated Bax and PUMA expression in both A2780 and A2780cis cells. In conclusion, trans-(±)-kusunokinin suppressed ovarian cancer cells through the inhibition of colony formation, cell proliferation and the induction of apoptosis. This pure compound could be a potential targeted therapy for ovarian cancer treatment in the future. However, studies in an animal model and clinical trial need to be performed to support the efficacy and safety of this new treatment.

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Section: Discussionmentioning

confidence: 51%

Effects of trans‑(±)‑kusunokinin on chemosensitive and chemoresistant ovarian cancer cells

et al. 2021

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“…TTK is overexpressed in cisplatin-resistant ovarian cancer cells and ovarian cancer patients with acquired resistance to cisplatin. TTK knockdown increases the sensitivity of cisplatin-resistant ovarian cancer cells to cisplatin via the PI3K/AKT signaling pathway [ 27 ]. Inhibition of TTK alters cell-cycle progression and exacerbates centrosome abnormalities, thus promoting the radiosensitivity of liver cancer cells in a p21-mediated manner [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

TTK Protein Kinase promotes temozolomide resistance through inducing autophagy in glioblastoma

Gao

Wei

et al. 2022

BMC Cancer

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Background Temozolomide (TMZ) resistance remains the main therapy challenge in patients with glioblastoma multiforme (GBM). TTK Protein Kinase (TTK) contributes to the radioresistance and chemoresistance in many malignancies. However, the role of TTK in the TMZ resistance of GBM cells remains unknown. Methods The expression of TTK was measured by western blot. The proliferation of GBM cells was assessed through MTT assay and clonogenic assay. Cell apoptosis was evaluated using western blot. LC3B puncta were detected using immunohistochemistry staining. The mouse xenograft model was used to investigate the role of TTK in vivo. Results Knockdown of TTK increased the sensitivity of GBM cells to TMZ treatment, while overexpression of TTK induced TMZ resistance. Two specific TTK inhibitors, BAY-1217389 and CFI-402257, significantly inhibited GBM cell proliferation and improved the growth-suppressive effect of TMZ. In addition, the knockdown of TTK decreased the autophagy levels of GBM cells. Inhibition of TTK using specific inhibitors could also suppress the autophagy process. Blocking autophagy using chloroquine (CQ) abolished the TMZ resistance function of TTK in GBM cells and in the mouse model. Conclusions We demonstrated that TTK promotes the TMZ resistance of GBM cells by inducing autophagy in vitro and in vivo. The use of a TTK inhibitor in combination with TMZ might help to overcome TMZ resistance and improve therapy efficiency in GBM.

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“…For instance, in the colorectal and glioblastoma in vitro models, the inhibition of TTK expression pharmacologically decreases cell viability, resulting in abnormal cell cycle progression, elevated aneuploidy, and induced apoptosis ( Yao et al, 2021 ). TTK activity is crucial for pancreatic cancer cell proliferation, making TTK a potential therapeutic target for new treatments ( Liu et al, 2021 ). Additionally, TTK was evaluated as a potential prognostic biomarker for triple-negative BC and it was demonstrated that increased TTK expression is associated with improved disease-free survival and OS, with a better prognosis ( Xu et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of gene expression profiles to identify differential prognostic factors of primary and metastatic breast cancer

Albogami

2022

Saudi Journal of Biological Sciences

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TTK is a potential therapeutic target for cisplatin-resistant ovarian cancer

Cited by 20 publications

References 29 publications

Effects of trans‑(±)‑kusunokinin on chemosensitive and chemoresistant ovarian cancer cells

Effects of trans‑(±)‑kusunokinin on chemosensitive and chemoresistant ovarian cancer cells

TTK Protein Kinase promotes temozolomide resistance through inducing autophagy in glioblastoma

Comprehensive analysis of gene expression profiles to identify differential prognostic factors of primary and metastatic breast cancer

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