Apoptosis, Cell Growth, and Glycogen Synthase Kinase 3β Phosphorylation in Caffeic Acid-Treated Human Malignant

Yoon-Jin Lee1,2, Ki Dam Kim3, Min Hyuk Choi3

  • 1Department of Biochemistry, Soonchunhyang University College of Medicine, Cheonan 31151, Republic of Korea.

Biomedicines
|October 29, 2025
PubMed

Insights

Caffeic acid (CA) shows anticancer effects against melanoma by activating the p53 pathway, not by affecting GSK3β signaling. This natural compound reduces melanoma cell viability and induces apoptosis.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Caffeic acid (CA), a phenolic compound, possesses antioxidant and anti-inflammatory properties with demonstrated anticancer activity.
  • The precise role of CA in melanoma and its impact on the GSK3β signaling pathway require further investigation.

Purpose of the Study:

  • To investigate the expression of phosphorylated GSK3β (p-GSK3β) in melanoma tissues.
  • To evaluate the anti-melanoma efficacy of caffeic acid (CA).

Main Methods:

  • Western blot analysis was used to quantify p-GSK3β levels in melanoma and normal skin samples.
  • G361 melanoma cells were treated with CA to assess cell viability, apoptosis, cell cycle, and signaling molecule expression.

Main Results:

  • Melanoma tissues exhibited significantly elevated levels of p-GSK3β compared to normal skin.
  • CA treatment reduced G361 melanoma cell viability, induced apoptosis, and increased p-GSK3β expression.
  • CA upregulated p53 and p21 while downregulating cyclin D1 and Bcl-2 in melanoma cells.

Conclusions:

  • Caffeic acid inhibits melanoma cell proliferation and induces apoptosis.
  • The anti-melanoma effects of CA are mediated through the activation of the p53 tumor suppressor pathway.
  • CA's mechanism does not appear to involve the modulation of GSK3β signaling in melanoma.

Related Concept Videos

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...
4.6K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.9K
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...
8.3K
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...
5.3K
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...
5.1K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.9K