We have reported previously the isolation of three photodynamic therapy (PDT)-resistant human colon carcinoma HT29 cell lines that show increased expression of the Hsp27 and BNip3 protein and a decreased expression of the mutant p53 protein compared to parental HT29 cells. Since mutant p53 and increased expression of Hsp27 have been associated with resistance to various chemotherapeutic agents, whereas BNip3 is a potent inducer of apoptosis, we were interested in determining whether these PDT-resistant cells were cross-resistant to other cytotoxic agents. We report here that the PDT-resistant HT29 cell lines showed a significant increase in cisplatin sensitivity and an increase in both spontaneous and cisplatin-induced apoptosis compared to parental HT29 cells. In addition, the cisplatin sensitivity of the PDT-resistant HT29 variants and several other clonal variants of HT29 cells correlated with increased BNip3 and decreased mutant p53 protein levels, but not Hsp27 protein levels.
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http://dx.doi.org/10.1016/j.bbrc.2005.03.213 | DOI Listing |
Biomed Pharmacother
December 2024
Department of Pharmacy, College of Pharmacy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan, Gyeonggi-do 15588, Republic of Korea. Electronic address:
Colorectal malignancies associated with KRAS and TP53 mutations led us to investigate the effects of combination therapy targeting KRAS, MEK1, or PLK1 in colorectal cancer. MEK1 is downstream of RAS in the MAPK pathway, whereas PLK1 is a mitotic kinase of the cell cycle activated by MAPK and regulated by p53. Bioinformatics analysis revealed that patients with colorectal cancer had a high expression of MAP2K1 and PLK1.
View Article and Find Full Text PDFCurr Biol
December 2024
The Hormel Institute, University of Minnesota, Austin, MN 55912, USA; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:
Serine 31 is a phospho-site unique to the histone H3.3 variant; mitotic phospho-Ser31 is restricted to pericentromeric heterochromatin, and disruption of phospho-Ser31 results in chromosome segregation defects and loss of p53-dependant G cell-cycle arrest. Ser31 is proximal to the H3.
View Article and Find Full Text PDFJ Dev Biol
November 2024
Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Barth syndrome (BTHS) is a rare, infantile-onset, X-linked mitochondriopathy exhibiting a variable presentation of failure to thrive, growth insufficiency, skeletal myopathy, neutropenia, and heart anomalies due to mitochondrial dysfunction secondary to inherited TAFAZZIN transacetylase mutations. Although not reported in BTHS patients, male infertility is observed in several () mouse alleles and in a mutant. Herein, we examined the male infertility phenotype in a BTHS-patient-derived point-mutant knockin mouse () allele that expresses a mutant protein lacking transacetylase activity.
View Article and Find Full Text PDFThorac Cancer
December 2024
Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Concurrent mutations in tumor protein p53 (TP53) or Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2-pathway components are linked to poor outcomes in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), but the impact of triple mutations remains unclear. We report a case of EGFR-, TP53-, and Cullin 3 (CUL3)-mutant NSCLC in a 43-year-old woman with widespread metastases at diagnosis, including those in the contralateral lung, distant lymph nodes, pericardium, liver, bones, left adrenal gland, and brain. She received osimertinib as first-line therapy, but pericardial effusion and liver metastases progressed rapidly over 3 months, and she was switched to carboplatin and pemetrexed.
View Article and Find Full Text PDFJ Am Heart Assoc
December 2024
Department of Cardiology, Pulmonology, and Nephrology Yamagata University School of Medicine Yamagata Japan.
Background: Doxorubicin-induced cardiotoxicity is still an important medical problem associated with a high mortality rate in cancer survivors. p53 plays a key role in doxorubicin-induced cardiotoxicity. Diacylglycerol kinase ζ (Dgkζ), a 130-kDa enzyme abundant in cardiomyocytes, regulates the p53 protein expression level in neurons.
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