Pterostilbene Inhibits Human Multiple Myeloma Cells via ERK1/2 and JNK Pathway In Vitro and In Vivo

Abstract

Multiple myeloma (MM) is the second most common malignancy in the hematologic system, which is characterized by accumulation of plasma cells in bone marrow. Pterostilbene (PTE) is a natural dimethylated analog of resveratrol, which has anti-oxidant, anti-inflammatory and anti-tumor properties. In the present study, we examined the anti-tumor effect of PTE on MM cell lines both in vitro and in vivo using the cell counting kit (CCK)-8, apoptosis assays, cell cycle analysis, reactive oxygen species (ROS) generation, JC-1 mitochondrial membrane potential assay, Western blotting and tumor xenograft models. The results demonstrated that PTE induces apoptosis in the H929 cell line and causes cell cycle arrest at G0/G1 phase by enhancing ROS generation and reducing mitochondrial membrane potential. The anti-tumor effect of PTE may be caused by the activation of the extracellular regulated protein kinases (ERK) 1/2 and c-Jun N-terminal kinase (JNK) signaling pathways. Additionally, mice treated with PTE by intraperitoneal injection demonstrated reduced tumor volume. Taken together, the results of this study indicate that the anti-tumor effect of PTE on MM cells may provide a new therapeutic option for MM patients.

Pterostilbene inhibits nutrient metabolism and induces apoptosis through AMPK activation in multiple myeloma cells

“…Multiple studies have reported that natural products derived from plants are important sources of drugs that may offer significant treatment for the majority of cancer types, including colorectal and oral cancer ( 41 , 42 ). Consistent with previous studies, in which it was observed that PTE inhibited MM cell viability and induced cell cycle arrest through regulating the mitogen-activated protein kinase pathway ( 43 , 44 ), the present study demonstrated that the administration of PTE could induce MM apoptosis in vitro , and decrease tumor burden in vivo . Additionally, to the best of our knowledge, the present study was the first to report that PTE-induced MM apoptosis was metabolically dependent, via the activation of AMPK, in vitro and in vivo .…”

Apoptotic and Nonapoptotic Activities of Pterostilbene against Cancer

“…For evaluating anti-multiple myeloma effect of PS, H929 cells has been injected into the flanks of female NOD/SCID mice and treated with PS for 14 days via intraperitoneal injection. The results show that, compared to control animals, tumor volumes are significantly decreased in the PS-treated mice, indicating the potent anti-myeloma effect of PS in vivo [ 160 ].…”

Gnetin‐C and other resveratrol oligomers with cancer chemopreventive potential

“…In addition, chemical modifications of the backbone structure of resveratrol have been shown to improve its pharmacokinetic parameters. In addition to their increased bioavailability compared with resveratrol, methylated analogues have superior antitumor activities in various in vitro and in vivo systems, which appears to be consistent with reports using the naturally occurring methylated resveratrol pterostilbene and 3,5,4‐trimethoxy‐ trans ‐stilbene . Further studies, particularly in vivo , will be required as the next step in order to determine the suitability of these analogs as pharmacologic agents for possible clinical anticancer applications.…”