Article
Oncology
Nicola Lockwood, Silvia Martini, Ainara Lopez-Pardo, Katharina Deiss, Hendrika A. Segeren, Robert K. Semple, Ian Collins, Dimitra Repana, Mathias Cobbaut, Tanya Soliman, Francesca Ciccarelli, Peter J. Parker
Summary: G2 arrest is crucial for the faithful segregation of sister chromatids, and the p53-p21 signaling pathway plays an essential role in cell lines, patient-derived cells, and colorectal cancer organoids. In arrest-defective hTERT-positive cells, the PKC epsilon failsafe mechanism is engaged. In ALT-dependent cancer cells, a distinct form of p53-independent G2 arrest is mediated by BLM and Chk1.
Article
Biochemistry & Molecular Biology
Shigeaki Sunada, Hiroko Saito, Doudou Zhang, Zeyu Xu, Yoshio Miki
Summary: CDK1 inhibitors regulate cellular sensitivity to DNA damage by controlling cell cycle progression and DNA repair inhibition, providing insights for developing clinical strategies targeting CDK1 inhibition in tumor cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Oncology
Soo Fern L. Lee, Jayshree L. Hirpara, Jianhua Qu, Sanjiv K. Yadav, Karishma Sachaphibulkij, Shazib Pervaiz
Summary: A novel topoisomerase II alpha inhibitor, mercaptopyridine oxide (MPO), is reported to induce cell cycle arrest and senescence through different cell cycle regulators in different cell lines. The inhibition of topoisomerase II alpha is associated with ROS-mediated activation of ATM-Chk2 kinase axis, independent of p53 function. Additionally, the interaction between topoisomerase II alpha and Chk1 is important for decatenation checkpoint activation.
Article
Oncology
Andrew J. Massey
Summary: The study revealed that treatment with the Chk1 inhibitor led to a significant upregulation of BCL2A1 in U2OS cells, but not in HT29 cells.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Rahul Singh, Vijay Kumar Bhardwaj, Jatin Sharma, Pralay Das, Rituraj Purohit
Summary: This research explores plant-based semi-synthetic molecules as potential CHK1 inhibitors, analyzing key determinants for receptor binding and evaluating drug likeness based on toxicity and bioavailability. The computational strategy suggests Bch10 as a promising CHK1 inhibitor compared to top co-crystallized molecules, opening new possibilities for potent CHK1 inhibitors.
Article
Oncology
Jiajing Niu, Jiamei Wang, Qi Zhang, Zhihua Zou, Yushuang Ding
Summary: The study revealed that sublethal doses of cinobufagin suppressed the viability of cancer cells by inducing oxidative stress, leading to DNA damage and cell cycle regulation that ultimately resulted in the induction of apoptosis.
CANCER CELL INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Jiyeon Leem, Jeong Su Oh
Summary: In this study, researchers discovered that MDC1 plays a non-canonical role in controlling G2/M transition in mouse oocytes by regulating APC/C-Cdh1-mediated cyclin B1 degradation in response to DNA damage. They also found that MDC1 depletion impairs spindle assembly by decreasing the integrity of microtubule organizing centers (MTOCs). These findings provide new insights into the regulation of the G2/M DNA damage checkpoint and cell cycle control in oocytes.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Chemistry, Medicinal
Tingting Jin, Peipei Wang, Xiubing Long, Kailong Jiang, Pinrao Song, Wenbiao Wu, Gaoya Xu, Yubo Zhou, Jia Li, Tao Liu
Summary: In this study, a series of potent novel diaminopyrimidine CHK1 inhibitors were designed, synthesized, and evaluated. Compound 13 exhibited favorable CHK1 inhibition both in vitro and in vivo, showing potential as an anticancer therapeutic agent. Furthermore, compound 13 demonstrated robust inhibition of CHK1 autophosphorylation, indicating its promise as a CHK1 inhibitor.
Article
Medicine, Research & Experimental
Basudeb Das, Swapnil Sahoo, Bibekanand Mallick
Summary: This study reveals for the first time that HIWI2 acts as a tumor suppressor in fibrosarcoma by modulating the ROS/DNA damage/p53 pathway.
Article
Oncology
Fiifi Neizer-Ashun, Resham Bhattacharya
Summary: The DNA damage response relies on CHK1 kinase for maintaining genomic integrity, involving in processes such as DNA replication and mitotic progression. While CHK1 has potential in cancer therapy, it has yet to be fully realized clinically.
Article
Plant Sciences
Asmita Pal, Soumee Sengupta, Rita Kundu
Summary: This study confirms the ethnopharmacological anticancer role of T. racemosa, inhibiting the abnormal proliferation of cervical cancer cells SiHa by inducing G2/M-phase cell cycle arrest and apoptotic cell death. Oxidative stress-mediated double-stranded DNA damage leads to apoptotic cell death through multiple routes, including the PI3K/Akt/NFKB pathway. The abundant alkaloid content of T. racemosa is suggested as the probable responsible cytotoxic principle.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Oncology
Katarzyna Malarz, Jacek Mularski, Michal Kuczak, Anna Mrozek-Wilczkiewicz, Robert Musiol
Summary: Aromatic sulfonates based on quinazolines exhibit strong anticancer activity, showing high efficacy against a range of cancer cell lines with minimal impact on normal cell proliferation. They may serve as promising scaffolds for developing anticancer agents.
Review
Biochemistry & Molecular Biology
David A. Gillespie
Summary: Two recent reports demonstrate that heritable, gain-of-function mutations within the Chk1 C-terminal regulatory domain can cause female infertility. Treatment with selective Chk1 inhibitor drugs can rescue this mutation and allow embryos to develop normally.
Article
Genetics & Heredity
Teresa Brooks, Joanne Wayne, Andrew J. Massey
Summary: Chk1 inhibitors have significant biological effects on cancer cells, inducing a bystander effect that increases DNA damage or replication stress in cells not directly exposed to the inhibitor. However, this bystander effect may also contribute to toxicity in non-tumor cells by increasing DNA damage.
Article
Cell Biology
Gerald Lossaint, Andela Horvat, Veronique Gire, Katarina Bacevic, Karim Mrouj, Fabienne Charrier-Savournin, Virginie Georget, Daniel Fisher, Vjekoslav Dulic
Summary: The balance between p21 and Chk1 controls cyclin D-CDK activity during cell cycle arrest, with p21 activating RB in non-transformed cells and Chk1 maintaining its activity in cancer cells. The compromised G2 exit in cancer cells is associated with sustained Chk1 activity, delayed p21 induction, untimely cyclin E1 re-expression, and genome reduplication.
JOURNAL OF CELL SCIENCE
(2022)