Related Experiment Video

Updated: Apr 15, 2026

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

19.3K

FTY720 enhances TRAIL-mediated apoptosis by up-regulating DR5 and down-regulating Mcl-1 in cancer cells

Seon Min Woo1, Bo Ram Seo1, Kyoung-jin Min1

  • 1Department of Immunology, School of Medicine, Keimyung University, Dalseo-Gu, Daegu 704-701, South Korea.

Oncotarget
|April 7, 2015
PubMed

Insights

FTY720 (Fingolimod) combined with TRAIL induces cancer cell death, sparing normal cells. This combination upregulates DR5 and downregulates Mcl-1, enhancing apoptosis and reducing tumor growth.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • FTY720 (Fingolimod) acts as a sphingosine-1-phosphate (S1P) receptor antagonist and sphingosine kinase 1 inhibitor.
  • TRAIL (TNF-related apoptosis-inducing ligand) is known for its ability to induce apoptosis in cancer cells.

Purpose of the Study:

  • To investigate the synergistic effect of FTY720 and TRAIL on cancer cell apoptosis.
  • To elucidate the molecular mechanisms underlying the combined treatment's efficacy.

Main Methods:

  • Treatment of human renal, breast, and colon carcinoma cells with FTY720 and TRAIL.
  • Assessment of apoptosis induction and tumor growth in xenograft models.
  • Analysis of death receptor 5 (DR5) and Mcl-1 expression at the post-translational level.

Main Results:

  • The combination of FTY720 and TRAIL induced apoptosis in human cancer cells but not in normal cells.
  • Combined treatment significantly reduced tumor growth in xenograft models.
  • FTY720 upregulated DR5 and downregulated Mcl-1 expression post-translationally, which were critical for apoptosis induction.

Conclusions:

  • FTY720 enhances TRAIL-induced apoptosis in human cancer cells by upregulating DR5 and downregulating Mcl-1.
  • The combination therapy shows potential as a cancer treatment strategy with selectivity for malignant cells.
Keywords:
DR5FTY720Mcl-1TRAILapoptosis

More Related Videos

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics12:28

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics

Published on: January 11, 2019

7.9K
Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer04:20

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer

Published on: February 9, 2024

1.6K

Related Concept Videos

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...
9.3K
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...
5.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.8K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
8.0K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.4K
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...
5.5K