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20 February 2019 : Laboratory Research  

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

Li Yingchun1DEF, Wang Huihan1DEF, Zhang Rong1DE, Zhang Guojun1DEF, Yang Ying1CDEF, Liu Zhuogang1ADFG*

DOI: 10.12659/MSM.913397

Med Sci Monit 2019; 25:1355-1361

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.

Keywords: Autophagy, Cell Migration Assays, Multiple Myeloma, Reactive Oxygen Species, Antineoplastic Agents, Phytogenic, Apoptosis, Caspases, Effector, Cell Survival, China, Drug Resistance, Neoplasm, Neoplasm Invasiveness, STAT3 Transcription Factor, Triterpenes

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750