Related Experiment Video

Updated: Sep 30, 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

Raloxifene, a selective estrogen receptor modulator, induces apoptosis in androgen-responsive human prostate cancer

Isaac Yi Kim1, Do Hwan Seong, Byung-Chul Kim

  • 1Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland 20892, USA.

Cancer Research
|July 5, 2002
PubMed

Insights

Raloxifene, a selective estrogen receptor modulator, effectively induces programmed cell death (apoptosis) in LNCaP prostate cancer cells. This occurs independently of androgen receptor activity, suggesting a novel therapeutic pathway.

Area of Science:

  • Oncology
  • Pharmacology
  • Cell Biology

Background:

  • Raloxifene is a selective estrogen receptor (ER) modulator with known benefits in osteoporosis and breast cancer prevention.
  • Prostate cancer cells, specifically the LNCaP cell line, express ER-beta, suggesting a potential role for ER modulators.
  • Tamoxifen has previously been shown to induce apoptosis in LNCaP cells.

Purpose of the Study:

  • To investigate the effect of raloxifene on the androgen-sensitive human prostate cancer cell line LNCaP.
  • To determine if raloxifene induces apoptosis in LNCaP cells and elucidate the underlying mechanism.
  • To assess the impact of raloxifene on androgen receptor activity in LNCaP cells.

Main Methods:

  • LNCaP cells were treated with varying concentrations of raloxifene.
  • Apoptosis was assessed using the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay.
  • Caspase activation was evaluated via immunoblotting, and cellular morphology changes were observed.
  • Androgen receptor activity was measured using prostate-specific antigen (PSA) assays and reporter gene assays (pARE-luciferase).

Main Results:

  • Raloxifene treatment resulted in a dose-dependent increase in LNCaP cell death, confirmed as apoptosis by TUNEL assay.
  • Apoptosis induction was mediated by caspase-9 activation, as evidenced by inhibition with a caspase-9 specific inhibitor (Z-LEHD-FMK).
  • Raloxifene did not significantly affect androgen receptor activity in LNCaP cells, despite their mutated AR and proliferation in anti-androgens.

Conclusions:

  • Raloxifene induces apoptosis in the androgen-sensitive LNCaP prostate cancer cell line.
  • The observed apoptosis is mediated through an androgen-independent pathway involving caspase-9 activation.
  • These findings suggest raloxifene as a potential therapeutic agent for prostate cancer, acting via ER-beta signaling.

More Related Videos

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

Related Concept Videos

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...
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...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
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 reduction of the tissue.