Tanshinone IIA arrests cell cycle and induces apoptosis in 786-O human renal cell carcinoma cells

Zou

et al. 2015

Arch Gynecol Obstet

Section: Discussionsupporting

confidence: 84%

Tanshinone IIA inhibits the proliferation, migration and invasion of ectopic endometrial stromal cells of adenomyosis via 14-3-3ζ downregulation

Zou

et al. 2015

Arch Gynecol Obstet

“…Tung’s study found that in the human lung adenocarcinoma cell lines (A549, CL1-0, and CL1-5), tanshinone IIA was likely to slow the progression of S to G2 phases of the cell cycle [17]. The similar results were found in the renal cancer cell line 786-O cells, the percentage of cells in S phase was increased in a dose-dependent manner with the tanshinone IIA treatment (0, 6.79, 13.59 or 27.18 μM, 24 h) [18]. Wang’s research team found that co-treatment of ADM (0.75 μM, 48 h) and itraconazole (6 μM, 48 h) brought about a notable increase in G2 phase and a decrease in G1 and S phase in the acute myeloid leukemia cells KG1α [19].…”

Section: Discussionmentioning

confidence: 61%

Tanshinone IIA combined with adriamycin inhibited malignant biological behaviors of NSCLC A549 cell line in a synergistic way

Xie

Liu

et al. 2016

BMC Cancer

BackgroundThe study was designed to develop a platform to verify whether the extract of herbs combined with chemotherapy drugs play a synergistic role in anti-tumor effects, and to provide experimental evidence and theoretical reference for finding new effective sensitizers.MethodsInhibition of tanshinone IIA and adriamycin on the proliferation of A549, PC9 and HLF cells were assessed by CCK8 assays. The combination index (CI) was calculated with the Chou-Talalay method, based on the median-effect principle. Migration and invasion ability of A549 cells were determined by wound healing assay and transwell assay. Flow cytometry was used to detect the cell apoptosis and the distribution of cell cycles. TUNEL staining was used to detect the apoptotic cells. Immunofluorescence staining was used to detect the expression of Cleaved Caspase-3. Western blotting was used to detect the proteins expression of relative apoptotic signal pathways. CDOCKER module in DS 2.5 was used to detect the binding modes of the drugs and the proteins.ResultsBoth tanshinone IIA and adriamycin could inhibit the growth of A549, PC9, and HLF cells in a dose- and time-dependent manner, while the proliferative inhibition effect of tanshinone IIA on cells was much weaker than that of adriamycin. Different from the cancer cells, HLF cells displayed a stronger sensitivity to adriamycin, and a weaker sensitivity to tanshinone IIA. When tanshinone IIA combined with adriamycin at a ratio of 20:1, they exhibited a synergistic anti-proliferation effect on A549 and PC9 cells, but not in HLF cells. Tanshinone IIA combined with adriamycin could synergistically inhibit migration, induce apoptosis and arrest cell cycle at the S and G2 phases in A549 cells. Both groups of the single drug treatment and the drug combination up-regulated the expressions of Cleaved Caspase-3 and Bax, but down-regulated the expressions of VEGF, VEGFR2, p-PI3K, p-Akt, Bcl-2, and Caspase-3 protein. Compared with the single drug treatment groups, the drug combination groups were more statistically significant. The molecular docking algorithms indicated that tanshinone IIA could be docked into the active sites of all the tested proteins with H-bond and aromatic interactions, compared with that of adriamycin.ConclusionsTanshinone IIA can be developed as a novel agent in the postoperative adjuvant therapy combined with other anti-tumor agents, and improve the sensibility of chemotherapeutics for non-small cell lung cancer with fewer side effects. In addition, this experiment can not only provide a reference for the development of more effective anti-tumor medicine ingredients, but also build a platform for evaluating the anti-tumor effects of Chinese herbal medicines in combination with chemotherapy drugs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2921-x) contains supplementary material, which is available to authorized users.

“…However, the effect of Tan IIA on the cell cycle distribution is still controversial. Different results were found using the renal cancer cell line 786‐O, for which the percentage of cells in S phase was increased in a dose‐dependent manner response to Tan IIA treatment (0, 6.79, 13.59, or 27.18 μM, 24 hr; Wei, Zhou, Hu, & Huang, ). These findings showed that low dosage Tan IIA might contribute to the cell cycle arrest at G1 phase, whereas high dosage Tan IIA might lead to S phase cell cycle blockage, which remains to be further explored.…”

Section: Discussionmentioning

confidence: 89%

Tanshinone IIA combined with cisplatin synergistically inhibits non‐small‐cell lung cancer in vitro and in vivo via down‐regulating the phosphatidylinositol 3‐kinase/Akt signalling pathway

Liao

Gao

Huang

et al. 2019

Phytotherapy Research

Cisplatin represents one of the first‐line drugs used for non‐small‐cell lung cancer treatment. However, considerable side effects and the emergence of drug resistance are becoming critical limitations to its application. Combinatorial strategies may be able to extend the use of cisplatin. Both Tanshinone IIA and cisplatin inhibit non‐small‐cell lung cancer cell growth in a time‐ and dose‐dependent manner. When Tanshinone IIA was combined with cisplatin at a ratio of 20:1, they were observed to exert a synergistic inhibitory effect on non‐small‐cell lung cancer cells. The combination treatment was shown to impair cell migration and invasion, arrest the cell cycle in the S phases, and induce apoptosis in A549 and PC9 cells in a synergistic manner. KEGG pathway analysis and molecular docking indicated that Tanshinone IIA might mainly influence the phosphatidylinositol 3‐kinase‐Akt signalling pathway. In all treated groups, the expression levels of Bax and cleaved Caspase‐3 were up‐regulated, whereas the expression levels of Bcl‐2, Caspase‐3, p‐Akt, and p‐PI3K proteins were down‐regulated. Among these, the combination of Tan IIA and cisplatin exhibited the most significant difference. Tanshinone IIA may function as a novel option for combination therapy for non‐small‐cell lung cancer treatment.