Low Doses of Cisplatin Induce Gene Alterations, Cell Cycle Arrest, and Apoptosis in Human Promyelocytic Leukemia Cells

Velma, Venkatramreddy; Dasari, Shaloam; Tchounwou, Paul B.

doi:10.4137/bmi.s39445

Cited by 66 publications

(40 citation statements)

References 62 publications

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“…In addition, as indicated by their ability to prevent digestion of plasmid DNA with BamHI restriction nuclease, the studied chromanone/flavanone analogues appear to be capable of intercalating with genomic DNA of cancer cells, thus leading to cell damage and ultimately apoptosis. It is noteworthy that commercially-used anticancer drugs, such as docetaxel, doxorubicin, cisplatin or etoposide, are also known to arrest the cycle of cancer cells in the G2/M phase [32][33][34]. Our findings correspond closely with those of previous reports on the cell cycle distribution in HL-60 cells following treatment with cisplatin.…”

Section: Discussionsupporting

confidence: 91%

Biological Evaluation of 3-Benzylidenechromanones and Their Spiropyrazolines-Based Analogues

et al. 2020

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A series of 3-benzylidenechrmanones 1, 3, 5, 7, 9 and their spiropyrazoline analogues 2, 4, 6, 8, 10 were synthesized. X-ray analysis confirms that compounds 2 and 8 crystallize in a monoclinic system in P21/n space groups with one and three molecules in each asymmetric unit. The crystal lattice of the analyzed compounds is enhanced by hydrogen bonds. The primary aim of the study was to evaluate the anti-proliferative potential of 3-benzylidenechromanones and their spiropyrazoline analogues towards four cancer cell lines. Our results indicate that parent compounds 1 and 9 with a phenyl ring at C2 have lower cytotoxic activity against cancer cell lines than their spiropyrazolines analogues. Analysis of IC50 values showed that the compounds 3 and 7 exhibited higher cytotoxic activity against cancer cells, being more active than the reference compound (4-chromanone or quercetin). The results of this study indicate that the incorporation of a pyrazoline ring into the 3-arylideneflavanone results in an improvement of the compounds’ activity and therefore it may be of use in the search of new anticancer agents. Further analysis allowed us to demonstrate the compounds to have a strong inhibitory effect on the cell cycle. For instance, compounds 2, 10 induced 60% of HL-60 cells to be arrested in G2/M phase. Using a DNA-cleavage protection assay we also demonstrated that tested compounds interact with DNA. All compounds at the concentrations corresponding to cytotoxic properties are not toxic towards red blood cells, and do not contribute to hemolysis of RBCs.

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Section: Discussionsupporting

confidence: 91%

Biological Evaluation of 3-Benzylidenechromanones and Their Spiropyrazolines-Based Analogues

et al. 2020

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“…However, the referenced studies were conducted at lower concentration of CDDP applied for only two hours and these observations were made during several days after the drug exposure (40,41,43,45). With increasing dose of the drug and longer periods of exposure this influence could not be showed so clearly due to high concentration of cells in sub-G 0 phase indicating that the cells might undergo apoptosis (46). Similar results were achieved in this study, where, due to high concentrations of CDDP used for a long period of time, the percentage of cells in sub-G 0 phase significantly increased, and the percentage of cells in G 0 /G 1 significantly decreased.…”

Section: Discussionmentioning

confidence: 99%

Complex of Platinum(II) with Tris(2-carboxyethyl)phosphine Induces Apoptosis in Canine Lymphoma/Leukemia Cell Lines

Henklewska

Pawlak

Pruchnik

et al. 2017

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“…It is worth noting that due to cisplatin-induced genotoxic stress, multiple signaling pathways that may contribute to apoptosis or to the development of chemoresistance are activated. Among others, protein kinase C, mitogen-activated protein kinases and the PI3-K/AKT pathway seem to play critical roles in the cisplatin effect on cancer cell function [ 3 – 6 ].…”

Section: Introductionmentioning

confidence: 99%

Cisplatin-induced ERK1/2 activity promotes G1 to S phase progression which leads to chemoresistance of ovarian cancer cells

et al. 2018

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The link between ERK1/2 activity and cisplatin cytotoxicity, in association with the cell cycle, in ovarian cancer cell lines resistant (A2780cis; SK-OV-3) and sensitive (A2780) to cisplatin was determined. We observed that cisplatin, at a low concentration enhanced the activation of ERK1/2 in A2780 cells and increased their accumulation in the S phase, resulting in low cytotoxicity. A high concentration of drug induced dephosphorylation and degradation of ERK1/2 and was extremely toxic, accumulating most of to these cells in the sub-G1 phase. The PD98059, pharmacological inhibitor of ERK1/2 activation, increased the cytotoxicity of cisplatin applied at a low concentration to A2780 cells (decreased ERK1/2 activity), causing shift of cell accumulation from the S to G1 phase. Surprisingly, PD98059 enhanced cell viability when a chemotherapeutic was used at high concentration, intensifying phosphorylation level of ERK1/2 and reversing cell cycle arrest in sub-G1 to promote the G1 and S phases. A2780cis cells demonstrated resistance to cisplatin with high ERK1/2 activity and accumulation of cells in the G1 and S phases. PD98059 sensitized resistant cells to drug toxicity during the first 24 hours of treatment, with blocked ERK1/2 phosphorylation and prevented progression from the G1 to S phase. SK-OV-3 resistant cells characterized with extremely high basal phosphorylation of ERK1/2, which wasn't changed after exposure to cisplatin. Administration of PD98059 didn't change the cytotoxicity of cisplatin in these cells. In conclusion, ERK1/2, activated by cisplatin, participates in the cell cycle progression from the G1 to S phase, enhancing cells’ survival and drug resistance.

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Low Doses of Cisplatin Induce Gene Alterations, Cell Cycle Arrest, and Apoptosis in Human Promyelocytic Leukemia Cells

Cited by 66 publications

References 62 publications

Biological Evaluation of 3-Benzylidenechromanones and Their Spiropyrazolines-Based Analogues

Biological Evaluation of 3-Benzylidenechromanones and Their Spiropyrazolines-Based Analogues

Complex of Platinum(II) with Tris(2-carboxyethyl)phosphine Induces Apoptosis in Canine Lymphoma/Leukemia Cell Lines

Cisplatin-induced ERK1/2 activity promotes G1 to S phase progression which leads to chemoresistance of ovarian cancer cells

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