Tanshinone IIA reduces SW837 colorectal cancer cell viability via the promotion of mitochondrial fission by activating JNK-Mff signaling pathways

Abstract

BackgroundMitochondrial homeostasis has been increasingly viewed as a potential target of cancer therapy, and mitochondrial fission is a novel regulator of mitochondrial function and apoptosis. The aim of our study was to determine the detailed role of mitochondrial fission in SW837 colorectal cancer cell viability, mobility and proliferation. In addition, the current study also investigated the therapeutic impact of Tanshinone IIA (Tan IIA), a type of anticancer adjuvant drug, on cancer mitochondrial homeostasis.ResultsThe results of our data illustrated that Tan IIA promoted SW837 cell death, impaired cell migration and mediated cancer proliferation arrest in a dose-dependent manner. Functional investigation exhibited that Tan IIA treatment evoked mitochondrial injury, as witnessed by mitochondrial ROS overproduction, mitochondrial potential collapse, antioxidant factor downregulation, mitochondrial pro-apoptotic protein upregulation, and caspase-9-dependent apoptotic pathway activation. Furthermore, we confirmed that Tan IIA mediated mitochondrial damage by activating mitochondrial fission, and the inhibition of mitochondrial fission abrogated the proapoptotic effects of Tan IIA on SW837 cells. To this end, our results demonstrated that Tan IIA modulated mitochondrial fission via the JNK-Mff pathways. The blockade of the JNK-Mff axis inhibited Tan IIA-mediated mitochondrial fission and promoted the survival of SW837 cells.ConclusionsAltogether, our results identified mitochondrial fission as a new potential target to control cancer viability, mobility and proliferation. Furthermore, our findings demonstrate that Tan IIA is an effective drug to treat colorectal cancer by activating JNK-Mff-mitochondrial fission pathways.Electronic supplementary materialThe online version of this article (10.1186/s12860-018-0174-z) contains supplementary material, which is available to authorized users.

Hypoxia-Induced ROS Promotes Mitochondrial Fission and Cisplatin Chemosensitivity via HIF-1α/Mff Regulation

“…31 Furthermore, Mff-induced mitochondrial fission was attributed to decreased colorectal cancer cell viability. 32 Our findings showed that Mff was a key molecule participating in mitochondrial fission, contributing to CDDP sensitivity in hypoxia-cultured HNSCC cells. Both Mff and Mfn2 expression were upregulated in HNSCC tissues, indicating that mitochondrial dynamics in tumor tissues are more active than that in normal tissues.…”

Hypoxia-Induced ROS Promotes Mitochondrial Fission and Cisplatin Chemosensitivity via HIF-1α/Mff Regulation

“…[29] Furthermore, Mff-induced mitochondrial ssion was attributed to decreased colorectal cancer cell viability. [30] Our ndings showed that Mff was a key molecule participating in mitochondrial ssion, contributing to CDDP sensitivity in hypoxia-cultured HNSCC cells. Both Mff and Mfn2 expression were upregulated in HNSCC tissues, indicating that mitochondrial dynamics in tumor tissues are more active than that in normal tissues.…”

Network Pharmacology Validation of Therapeutic Mechanisms of Tanshinone IIA in Colorectal Cancer

“…One of the most important bioactive constituent of the medicinal plant Salvia miltiorrhiza is Tan IIA, which has been widely used in the treatment of cardiovascular, cerebrovascular, and neoplastic disorders. [17][18][19] As mentioned, this compound exhibits multiple anti-neoplastic mechanisms, including inhibiting tumor cell proliferation, 20 invasion, and metastasis, 21 and induction of apoptosis. 22 However, the therapeutic molecular mechanisms of Tan IIA in the context of CRC remain incompletely known.…”