Tanshinone I inhibited growth of human chronic myeloid leukemia cells via JNK/ERK mediated apoptotic pathways

Abstract

Tanshinone I (Tan I) is one of the main bioactive ingredients derived from Salvia miltiorrhiza Bunge, which has exhibited antitumor activities toward various human cancer cells. However, its effects and underlying mechanisms on human chronic myeloid leukemia (CML) cells still require further investigation. This study determined the effects and mechanisms of antiproliferative and apoptosis induction activity induced by Tan I against K562 cells. The cytotoxic effect of Tan I at varying concentrations on K562 cells was evaluated via MTT assay. Cell apoptosis was further investigated through DAPI staining and flow cytometry analysis. The expression levels of apoptosis-related proteins and activities of JNK/ATF2 and ERK signaling pathways were analyzed by western blot. Quantitative PCR was performed to further determine mRNA expression levels of JNK1/2 and ERK1/2 after Tan I treatment. The results indicated that Tan I significantly inhibited K562 cell growth and induced apoptosis in a concentration-and time-dependent manner. It induced significant cellular morphological changes and increased apoptosis rates in CML cells. Tan I promoted the cleavages of caspase-related proteins, as well as increased the expression levels of PUMA. Furthermore, Tan I significantly activated JNK and inhibited ATF-2 and ERK signaling pathways. The mRNA expression levels of JNK1/2 and ERK1/2 were up-regulated by Tan I, further confirming its regulatory effects on JNK/ERK signaling pathways. Overall, our results indicated that Tan I suppressed cell viability via JNK-and ERK-mediated apoptotic pathways in K562 cells, suggesting that it might be a promising candidate as a novel anti-leukemia drug.

Tanshinone IIA and hepatocellular carcinoma: A potential therapeutic drug

“…This protein can activate some genes involved in cell proliferation regulation in the MAPK pathway, such as Ras, Raf, ERK, and JNK, to increase proliferation and inhibit apoptosis ( 153 – 155 ). However, TsIIA not only directly inhibits the expression and phosphorylation of MAPK ( 156 ), but also inhibits the activation and expression of related molecules in its mediated signal pathway, including ERK, JNK, p38 MAPK, etc. ( 157 ).…”

“…The galactose modified PH sensitive Niosomes developed by Hu X et al. can not only target the liver, but also significantly prolong the blood circulation time of TsIIA, and also found that the strength of this ability is positively related to the content of galactose ( 156 ). It is worth mentioning that the existence of mixed micelles also enhances the possibility of developing TsIIA anti liver cancer drugs ( 30 ).…”

Salvia miltiorrhiza in cancer: Potential role in regulating MicroRNAs and epigenetic enzymes

“…Apoptosis is an autonomous and orderly cell death process controlled by genes that occurs after cells are stimulated by physiological or pathological signals, and tumors have the ability to resist apoptosis via multiple strategies ( Pistritto et al, 2016 ; Huang et al, 2021a ). The antitumor effect of S. miltiorrhiza bioactive compounds has been linked to the induction of apoptosis in multiple studies ( Sun et al, 2021 ). For example, tan IIA induces apoptosis of ovarian cancer A2780 cells by regulating the PI3K/Akt/c-Jun N-terminal kinase (JNK) signaling pathway, which increases the expression of caspase 3, caspase 8, and caspase 9 but decreases the expression of B cell lymphoma 2 (Bcl-2) family proteins (Bcl-w and Bcl-1L) ( Zhang et al, 2019a ).…”