Related Experiment Video

Updated: Aug 7, 2026

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer
09:40

Tropomodulin 3 Overexpression as a Marker for Platinum Resistance and Immune Infiltration in Ovarian Cancer

Published on: August 2, 2024

Azidothymidine and cisplatin increase p14ARF expression in OVCAR-3 ovarian cancer cell line

Liisa Vaskivuo1, Jaana Rysä, Johanna Koivuperä

  • 1Department of Pharmacology and Toxicology, University of Oulu, FI-90014 Oulu, Finland.

Toxicology and Applied Pharmacology
|June 27, 2006
PubMed

Insights

Azidothymidine (AZT) and cisplatin (CDDP) can induce the p14ARF protein in ovarian cancer cells, even with mutated p53. This suggests p14ARF responds to DNA damage independently of oncogene activation.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Stress Response

Background:

  • The p14ARF tumor suppressor regulates p53 by inhibiting mdm2-p53 interaction.
  • p14ARF is activated by oncogenic stimuli, but its response to cellular stress and DNA damage is not well understood.
  • Azidothymidine (AZT) is under investigation as an anticancer chemotherapy enhancer, yet its effects on the p53 pathway are largely unknown.

Purpose of the Study:

  • To investigate the effects of AZT, cisplatin (CDDP), and docetaxel (DTX) on the p14ARF pathway in ovarian carcinoma cells.
  • To determine if p14ARF responds to DNA damage in cell lines with non-functional p53.
  • To explore the relationship between AZT and cellular pathways, specifically the p53 pathway.

Main Methods:

  • Treatment of ovarian carcinoma cell lines (OVCAR-3, A2780) and breast carcinoma cells (MCF-7) with AZT, CDDP, and DTX.
  • Analysis of p53 and p14ARF protein and mRNA expression levels.
  • Investigation of cell death and oncoprotein levels (c-Myc, H-ras).

Main Results:

  • AZT, CDDP, and DTX induced distinct molecular responses in OVCAR-3 cells (mutated p53).
  • In cells with wild-type p53 (A2780, MCF-7), all drugs elicited similar p53 responses.
  • DTX down-regulated p14ARF in OVCAR-3 cells, while AZT and a short CDDP pulse induced it.
  • CDDP and AZT increased p14ARF mRNA in OVCAR-3 cells.
  • HT-29 colon carcinoma cells (mutated p53) showed p14ARF down-regulation with all treatments.
  • Differences in cell death did not correlate with observed protein and mRNA expression changes.
  • AZT or CDDP treatment did not increase c-Myc or H-ras levels in OVCAR-3 cells.

Conclusions:

  • p14ARF exhibits differential responses to AZT, CDDP, and DTX in ovarian carcinoma cells, influenced by p53 status.
  • Endogenous p14ARF can respond to DNA damage in cell lines lacking functional p53, independent of oncogene activation.
  • AZT and CDDP show potential to modulate the p14ARF pathway in cancer cells with mutated p53.

More Related Videos

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity04:20

Knockdown of FAM83A to Verify Its Role in Cervical Cancer Cell Growth and Cisplatin Sensitivity

Published on: February 9, 2024

Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines11:50

Enrichment for Chemoresistant Ovarian Cancer Stem Cells from Human Cell Lines

Published on: September 10, 2014

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...