Antitumor Activity of Asiaticoside Against Multiple Myeloma Drug-Resistant Cancer Cells Is Mediated by Autophagy Induction, Activation of Effector Caspases, and Inhibition of Cell Migration, Invasion, and STAT-3 Signaling Pathway

Med Sci Monit. 2019 Feb 20:25:1355-1361. doi: 10.12659/MSM.913397.

Abstract

BACKGROUND Accumulating evidence suggests that plant-derived molecules may prove extremely beneficial in the development of chemotherapy for deadly cancer types. Multiple myeloma is a rare and incurable type of cancers. Very little research has been directed towards the development of chemotherapy for the management of multiple myeloma. Here, the anticancer effects of a plant-derived triterpenoid, Asiaticoside, were examined against the drug-resistant myeloma cell line KM3/BTZ. MATERIAL AND METHODS Cell viability was determined by CCK-8 assay and autophagy was checked by transmission electron microscopy. ROS levels were determined by flow cytometery. Cell migration and invasion were examined by Transwell assay. Protein expression was assessed by Western blotting. RESULTS The results showed that Asiaticoside inhibits the growth of the KM3/BTZ cells and exhibited an IC₅₀ of 12 µM. Further, it was observed that the anticancer effects of Asiaticoside are due to the induction of autophagy allied with upsurge of the expression of LC3-II. Moreover, the expression of the effector caspases in the KM3/BTZ cells was also altered. Asiaticoside also caused accretion of the ROS in the KM3/BTZ cells and inhibited their migratory and invasive properties via modulation of the STAT-3 signaling pathway. CONCLUSIONS Asiaticoside may prove useful in the management and treatment of the multiple myeloma and needs further investigation.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Caspases, Effector / drug effects
  • Cell Line, Tumor / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • China
  • Drug Resistance, Neoplasm / drug effects
  • Humans
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / metabolism*
  • Neoplasm Invasiveness
  • Reactive Oxygen Species
  • STAT3 Transcription Factor / drug effects
  • Signal Transduction / drug effects
  • Triterpenes / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Reactive Oxygen Species
  • STAT3 Transcription Factor
  • Triterpenes
  • Caspases, Effector
  • asiaticoside