DAP1 negatively regulates autophagy induced by cardamonin in SKOV3 cells

Xuekun Nie1, Huajiao Chen2, Peiguang Niu2

  • 1Department of Pharmacy, Ningde Municipal Hospital, Affiliated Hospital of Fujian Medical University, Ningde, Fujian, China.

Insights

Cardamonin induces autophagy and inhibits ovarian cancer cell proliferation by targeting mammalian target of rapamycin (mTOR). Death-associated protein 1 (DAP1) negatively regulates this process, suggesting DAP1 as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Autophagy plays a critical role in human tumor development, including ovarian cancer.
  • Mammalian target of rapamycin (mTOR) is a key regulator of autophagy.
  • Cardamonin, a plant-derived flavonoid, induces autophagy and inhibits cancer cell proliferation, but its mechanism is not fully understood.

Purpose of the Study:

  • To investigate the role of death-associated protein 1 (DAP1) in cardamonin-induced autophagy and proliferation inhibition in tumor cells.
  • To explore the potential of DAP1 as a therapeutic target for ovarian cancer.

Main Methods:

  • Bioinformatic analysis of DAP1 expression in ovarian cancer patients.
  • In vitro studies using SKOV3 ovarian cancer cells.
  • Manipulation of DAP1 expression using small interfering RNA (siRNA).
  • Assessment of autophagy induction, mTOR signaling, and cell proliferation.

Main Results:

  • DAP1 expression correlates with patient survival in ovarian cancer.
  • Cardamonin-induced autophagy is linked to mTOR inhibition.
  • DAP1 silencing reduced cell proliferation and enhanced cardamonin's antiproliferative effects.
  • DAP1 silencing elevated autophagy levels and increased autophagy flux in response to cardamonin.

Conclusions:

  • DAP1 negatively regulates cardamonin-induced autophagy.
  • DAP1 plays a role in ovarian cancer cell proliferation and response to cardamonin.
  • DAP1 represents a potential therapeutic target for ovarian cancer treatment.

Related Concept Videos

Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.1K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.5K
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
8.6K
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...
5.4K
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...
7.9K
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...
5.0K