Melatonin Sensitizes OVCAR-3 Cells to Cisplatin through Suppression of PI3K/Akt Pathway

Sahar Baghal-Sadriforoush1, Morteza Bagheri2, Isa Abdi Rad3

  • 1Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran. sbaghalsadriforoush@yahoo.com.

Insights

Melatonin enhances cisplatin

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Ovarian cancer remains a significant health challenge.
  • Understanding molecular pathways like PI3K/Akt is crucial for treatment.
  • Melatonin's role in cancer therapy is an area of active research.

Purpose of the Study:

  • To investigate melatonin's effects on oxidative stress and apoptosis in ovarian cancer cells.
  • To determine melatonin's impact on the PI3K/Akt signaling pathway.
  • To evaluate combination therapy with cisplatin and melatonin.

Main Methods:

  • Ovarian cancer cells (OVCAR3) were treated with cisplatin, melatonin, or both.
  • Reactive oxygen species (ROS) levels were measured.
  • Protein expression and signaling pathway activity (PI3K/Akt) were analyzed via Western blot.

Main Results:

  • Melatonin increased reactive oxygen species (ROS) and caspase 3 cleavage, indicating enhanced apoptosis.
  • Melatonin decreased Akt phosphorylation, suggesting PI3K/Akt pathway inhibition.
  • Combined cisplatin and melatonin therapy amplified apoptosis and oxidative stress.

Conclusions:

  • Melatonin potentiates cisplatin's anti-cancer effects in OVCAR3 cells.
  • The combination therapy inhibits the PI3K/Akt pathway and increases oxidative stress.
  • Melatonin shows promise as an adjuvant therapy for ovarian cancer.

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.9K
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...
4.6K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.8K
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...
3.9K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.7K
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...
4.9K