Calycosin induces apoptosis in osteosarcoma cell line via ERβ‑mediated PI3K/Akt signaling pathways

Wei Tian1, Zhi-Wei Wang1, Bao-Ming Yuan1

  • 1Department of Orthopedics, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia Autonomous Region 028007, P.R. China.

Insights

Calycosin, a phytoestrogen, inhibits osteosarcoma cell growth and promotes apoptosis. This effect is mediated through estrogen receptor beta (ERβ) by inhibiting the PI3K/Akt signaling pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Calycosin, a phytoestrogen, mimics estrogen and inhibits proliferation in estrogen-dependent cancers.
  • Estrogen receptor beta (ERβ) plays a role in ERβ-induced inhibition of PI3K/Akt signaling.

Purpose of the Study:

  • Investigate calycosin's effects on human osteosarcoma (OS) cells.
  • Examine the molecular mechanisms involving ERβ in calycosin's action on OS cells.

Main Methods:

  • Human OS MG-63 cells were treated with calycosin.
  • MTT and flow cytometry assays assessed proliferation and apoptosis.
  • Western blot analyzed protein expression of ERβ, p-PI3K, p-Akt, cleaved PARP, and cleaved caspase-3.

Main Results:

  • Calycosin inhibited proliferation and induced apoptosis in MG-63 cells.
  • ERβ expression increased with calycosin treatment; an ERβ inhibitor reversed these effects.
  • Calycosin downregulated p-PI3K and p-Akt, with reversal by the ERβ inhibitor.

Conclusions:

  • Calycosin inhibits osteosarcoma cell proliferation and induces apoptosis.
  • These effects are mediated by ERβ-dependent inhibition of the PI3K/Akt pathway.
  • ERβ influences downstream signaling of PARP1 and caspase-3, impacting cell fate.

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...
5.5K
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...
8.0K
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...
4.5K
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
13.5K
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...
7.8K
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
13.7K