Tanshinone IIA induces cytochrome c-mediated caspase cascade apoptosis in A549 human lung cancer cells via the JNK pathway

Abstract

Tanshinone IIA (TSIIA), a natural diterpene quinone in the traditional Chinese medicinal herb Dan-Shen (Salvia miltiorrhiza), has extensively exerted antitumor activity in cellular and animal models. However, the molecular mechanisms underlying the antitumor effects of TSIIA remain largely unknown. The in vitro effects of TSIIA on apoptosis were investigated in A549 non-small cell lung cancer (NSCLC) cells. The data showed that TSIIA significantly suppressed the proliferation of A549 cells in a dose-dependent manner, with IC50 values of 16.0±3.7 and 14.5±3.3 µM at 48 h as determined by Cell Counting Kit-8 (CCK-8) assay and clone formation assay, respectively. The change of mitochondrial morphology and the loss of mitochondrial membrane potential (MMP) were observed during the induction. Furthermore, TSIIA induced A549 cell apoptosis as confirmed by typical morphological changes, with cytochrome c release from the mitochondria and Bax translocation to the mitochondria. Caspase activity data indicated that TSIIA activated caspase-9 and caspase-3 of mitochondria-mediated apoptosis, but not caspase-8 of receptor-mediated apoptosis, which could be largely rescued by SP600125 (JNK inhibitor). Taken together, these findings provide the first evidence that TSIIA inhibits growth of NSCLC A549 cells, induces activation of JNK signaling and triggers caspase cascade apoptosis mediated by the release of cytochrome c, which provides a better understanding of the molecular mechanisms of TSIIA on lung cancer.

Tanshinone IIA enhances chemosensitivity of colon cancer cells by suppressing nuclear factor-κB

“…TSA has been demonstrated to exert an antitumor activity in numerous types of human cancer, including breast, lung, liver, prostate and ovarian cancer and leukemia (15,(21)(22)(23)(24)(25). The data of the present study showed that the exposure of the HCT1116 and COLO205 colon cancer cell lines to TSA greatly decreased their cell viability in a concentration-dependent manner (P<0.05; Fig.…”

“…In addition, Fu et al (25) found that TSA blocked the epithelial-mesenchymal transition through the downregulation of hypoxia-inducible factor-1α, reversing hypoxia-induced chemotherapy resistance in breast cancer cell lines. In addition, increasing evidence indicated that TSA can inhibit tumor cell growth and induce apoptosis (15,17,43); however, despite the fact that in certain type of cancer evidence showed that intrinsic apoptosis pathways were involved (14,44) (46) found that TSA potentiated the efficacy of 5-FU in colon cancer cells in vivo through the downregulation of P-glycoprotein and LC3-II. The results of the present study confirmed the antitumor activity and chemosensitizing effect of TSA in colon cancer cells and provided new evidence that TSA can sensitize colon cancer cells to 5-FU through the suppression of NF-κB activation.…”

The triplet state of tanshinone I and its synergic effect on the phototherapy of cancer cells with curcumin

“…By changing the concentration of Tan I, a series of observed decaying constants of 3 Bz ⁄ and observed forming constants of 3 Tan I ⁄ were obtained. The rate constant for the excited energy transfer from 3 Bz ⁄ to Tan I is (7.61 ± 0.46) * 10 9 M À1 S À1 according to the slope, as shown in Fig.…”

“…To determine the molar absorption coefficient of 3 Tan I ⁄ , we use 3 Bz ⁄ as a reference in the energy transfer reaction [16]. The energy transfer reaction from 3 Bz ⁄ to Tan I reached its balance at approximately 1 ls after the laser pulse, as shown in Fig.…”

“…There are two main components in Salvia miltiorrhiza Bunge, the lipophilic tanshinones and the hydrophilic phenolic acids. Most research has focused on tanshinone IIA because it can be used to cure a variety of cancers [3][4][5] and it is an excellent antioxidant in biologic tissue [6,7]. Recent studies have shown that it can reduce the risk of Alzheimer's disease [8] and has a neuroprotective effect [9,10].…”