Enhancement of cisplatin and etoposide cytotoxicity after all-trans retinoic-acid-induced cellular differentiation of a murine embryonal carcinoma cell line. 1993

H J Guchelaar, and H Timmer-Bosscha, and A Dam-Meiring, and D R Uges, and J W Oosterhuis, and E G de Vries, and N H Mulder
Department of Pharmacy, University Hospital of Groningen, The Netherlands.

The potential of a combination of differentiation induction and chemotherapy was analyzed. Treatment of the murine embryonal carcinoma (EC) cell line PCC4 in vitro with all-transretinoic acid (RA) was followed by exposure to cisplatin (CDDP) or etoposide (VP-16). The expression of EC-cell-specific markers decreased upon 96 hr exposure to 10(-9), 10(-8), 10(-7) and 10(-6) M RA, indicating a loss of embryonal phenotype of the cells, whereas expression of markers specific for cytokeratins and neurofilaments was increased after this treatment. These data suggest early somatic differentiation of PCC4 cells upon treatment with RA. Cellular growth rate of PCC4 cells was not affected by preincubation with RA at 10(-9) M for 96 hr, but was reduced at 10(-8) and 10(-7) M RA and inhibited at 10(-6) M RA. Culture of PCC4 cells in the presence of 10(-7) M RA for 96 hr led to accumulation in G1 of the cell cycle, whereas at 10(-8) M RA cell-cycle distribution was not affected. RA-treated and -untreated PCC4 cells were compared for CDDP and VP-16 sensitivity. Pre-treatment with 10(-9), 10(-8) and 10(-7) M RA increased CDDP sensitivity, resulting in a 1.9-, 2.7- and 2.6-fold decrease in the concentrations inhibiting survival by 50% (IC50s) respectively. Pre-treatment with 10(-8) and 10(-7) M RA increased VP-16 sensitivity 2.5- and 3.0-fold, respectively. Enhanced CDDP sensitivity at RA concentrations not affecting cell-cycle distribution was not attributable to changes in cellular platinum (Pt) accumulation, or to changes of Pt-DNA binding.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D009373 Neoplasms, Germ Cell and Embryonal Neoplasms composed of primordial GERM CELLS of embryonic GONADS or of elements of the germ layers of the EMBRYO, MAMMALIAN. The concept does not refer to neoplasms located in the gonads or present in an embryo or FETUS. Germ Cell Cancer,Germ Cell Tumor,Neoplasms, Embryonal and Mixed,Cancer, Embryonal,Cancer, Embryonal and Mixed,Embryonal Neoplasms,Germ Cell Neoplasms,Germ Cell and Embryonal Neoplasms,Germ Cell and Embryonic Neoplasms,Neoplasms, Embryonal,Neoplasms, Germ Cell,Neoplasms, Germ Cell and Embryonic,Cancer, Germ Cell,Cancers, Embryonal,Cancers, Germ Cell,Embryonal Cancer,Embryonal Cancers,Embryonal Neoplasm,Germ Cell Cancers,Germ Cell Tumors,Neoplasm, Embryonal,Tumor, Germ Cell,Tumors, Germ Cell
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002945 Cisplatin An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. Platinum Diamminodichloride,cis-Diamminedichloroplatinum(II),cis-Dichlorodiammineplatinum(II),Biocisplatinum,Dichlorodiammineplatinum,NSC-119875,Platidiam,Platino,Platinol,cis-Diamminedichloroplatinum,cis-Platinum,Diamminodichloride, Platinum,cis Diamminedichloroplatinum,cis Platinum
D004273 DNA, Neoplasm DNA present in neoplastic tissue. Neoplasm DNA
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005047 Etoposide A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. Demethyl Epipodophyllotoxin Ethylidine Glucoside,Celltop,Eposide,Eposin,Eto-GRY,Etomedac,Etopos,Etoposide Pierre Fabre,Etoposide Teva,Etoposide, (5S)-Isomer,Etoposide, (5a alpha)-Isomer,Etoposide, (5a alpha,9 alpha)-Isomer,Etoposide, alpha-D-Glucopyranosyl Isomer,Etoposido Ferrer Farma,Exitop,Lastet,NSC-141540,Onkoposid,Riboposid,Toposar,VP 16-213,VP-16,Vepesid,Vépéside-Sandoz,Eto GRY,Etoposide, alpha D Glucopyranosyl Isomer,NSC 141540,NSC141540,Teva, Etoposide,VP 16,VP 16 213,VP 16213,VP16,Vépéside Sandoz,alpha-D-Glucopyranosyl Isomer Etoposide
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000943 Antigens, Differentiation Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation. Differentiation Antigen,Differentiation Antigens,Differentiation Antigens, Hairy Cell Leukemia,Differentiation Marker,Differentiation Markers,Leu Antigen,Leu Antigens,Marker Antigen,Marker Antigens,Markers, Differentiation,Antigen, Differentiation,Antigen, Leu,Antigen, Marker,Antigens, Leu,Antigens, Marker,Marker, Differentiation

Related Publications

H J Guchelaar, and H Timmer-Bosscha, and A Dam-Meiring, and D R Uges, and J W Oosterhuis, and E G de Vries, and N H Mulder
February 1985, Experimental cell research,
H J Guchelaar, and H Timmer-Bosscha, and A Dam-Meiring, and D R Uges, and J W Oosterhuis, and E G de Vries, and N H Mulder
January 1998, Cancer chemotherapy and pharmacology,
H J Guchelaar, and H Timmer-Bosscha, and A Dam-Meiring, and D R Uges, and J W Oosterhuis, and E G de Vries, and N H Mulder
October 1996, Glycoconjugate journal,
H J Guchelaar, and H Timmer-Bosscha, and A Dam-Meiring, and D R Uges, and J W Oosterhuis, and E G de Vries, and N H Mulder
March 1987, Cell differentiation,
H J Guchelaar, and H Timmer-Bosscha, and A Dam-Meiring, and D R Uges, and J W Oosterhuis, and E G de Vries, and N H Mulder
September 2021, Biochemical and biophysical research communications,
H J Guchelaar, and H Timmer-Bosscha, and A Dam-Meiring, and D R Uges, and J W Oosterhuis, and E G de Vries, and N H Mulder
February 2007, Cancer research,
H J Guchelaar, and H Timmer-Bosscha, and A Dam-Meiring, and D R Uges, and J W Oosterhuis, and E G de Vries, and N H Mulder
March 2005, Biological & pharmaceutical bulletin,
H J Guchelaar, and H Timmer-Bosscha, and A Dam-Meiring, and D R Uges, and J W Oosterhuis, and E G de Vries, and N H Mulder
August 1999, Experimental hematology,
H J Guchelaar, and H Timmer-Bosscha, and A Dam-Meiring, and D R Uges, and J W Oosterhuis, and E G de Vries, and N H Mulder
December 1979, Experimental cell research,
H J Guchelaar, and H Timmer-Bosscha, and A Dam-Meiring, and D R Uges, and J W Oosterhuis, and E G de Vries, and N H Mulder
August 2020, Journal of clinical medicine,
Copied contents to your clipboard!