In vitro anti-carcinogenic effect of andarine as a selective androgen receptor modulator on MIA-PaCa-2 cells by decreased proliferation and cell-cycle arrest at G0/G1 phase

Biochem Biophys Res Commun. 2023 Sep 3:671:132-139. doi: 10.1016/j.bbrc.2023.06.016. Epub 2023 Jun 7.

Abstract

Pancreatic cancer (PC) continues to be devastating due to its highly malignant nature and poor prognosis. The limited benefits of the chemotherapeutic drugs and increasing resistance pose a critical challenge to overcome and warrant investigations for new therapeutic agents. Several preclinical and clinical studies have suggested a possible role of the androgen receptor (AR) signaling pathway in PC development and progression. Nevertheless, the studies are limited and inconclusive in explaining the molecular link between AR signaling and PC. Selective androgen receptor modulators (SARMs) are small molecule drugs with high affinity for the androgen receptor. SARMs elicit selective anabolic activities while abrogating undesired androgenic side effects. There is no study focusing on the utility of SARMs as inhibitors of PC. Here, we report the first study evaluating the possible anti-carcinogenic influences of andarine, a member of the SARMs, on PC. The data we presented here has illustrated that andarine repressed PC cell growth and proliferation via cell cycle arrest at G0/G1 phase. Gene expression analysis revealed that it downregulates CDKN1A expression level accordingly. Furthermore, we established that the anti-carcinogenic activity of andarine is not mediated by the PI3K/AKT/mTOR signaling pathway, a crucial regulator of cell survival. Our findings suggest that andarine might be considered as a prospective drug for PC.

Keywords: Anti-cancer agent; PI3K/AKT/mTOR; Pancreatic cancer; S4; Selective androgen receptor modulator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / pharmacology
  • Anticarcinogenic Agents* / pharmacology
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation
  • G1 Phase
  • Phosphatidylinositol 3-Kinases / metabolism
  • Receptors, Androgen* / metabolism

Substances

  • Receptors, Androgen
  • andarine
  • Anticarcinogenic Agents
  • Phosphatidylinositol 3-Kinases
  • Androgens