Tanshinone IIA induces cell death via Beclin-1-dependent autophagy in oral squamous cell carcinoma SCC-9 cell line.

Tanshinone IIA (TAN) is one of the major functional compounds of Salvia miltiorrhiza Bunge and possesses the ability to suppress the growth of multiple cancer cell types via its apoptosis- and autophagy-inducing functions. In this study, the effect of TAN therapy on the survival of oral squamous cell carcinoma (OSCC) was evaluated, and the underlying mechanism involved in the treatment was investigated. Human oral squamous cell carcinoma cell SCC-9 was used for in vitro assays and induction in an OSCC xenograft mouse model. The tumor cells were subjected to TAN administration at different concentrations. Then the apoptosis and autophagy processes in SCC-9 cells were evaluated and the activities of Beclin-1/Atg7/Atg12-Atg5 and PI3K/Akt/mTOR pathways were determined. In addition, by knocking down the expression of Beclin-1 in SCC-9 cells, the study also assessed the role of the indicator in the anti-OSCC effect of TAN. Results of in vitro assays were further validated with an OSCC xenograft mouse model. Administration of TAN-induced cell apoptosis and upregulated the expression of cleaved-caspase-3. Simultaneously, the autophagy process in SCC-9 cells was initiated by TAN, which was signaled by the formation of autophagosomes and increase in the ratio of LC3 II/LC3I. The above processes were associated with the activation of Beclin-1/Atg7/Atg12-Atg5 signaling and inhibition of PI3K/Akt/mTOR signaling. Our results also inferred a partially Beclin-1-dependent mechanism of action of TAN in OSCC cells: knockdown of the Beclin-1 blocked the effect of TAN on SCC-9 cells both in vivo and in vitro. Our study provided a preliminary explanation of the mechanism involved in TAN effect: the agent exerted its autophagy-inducing effect against OSCC in a multipronged manner, by both inducing the Beclin-1/Atg7/Atg12-Atg5 pathway and suppressing the PI3K/Akt/mTOR pathway.

Qiu Y ，Li C ，Wang Q ，Zeng X ，Ji P ... -  《Cancer Medicine》

Mechanisms of Tanshinone II a inhibits malignant melanoma development through blocking autophagy signal transduction in A375 cell.

Li X ，Li Z ，Li X ，Liu B ，Liu Z ... -  《BMC CANCER》

Tanshinone I attenuates the malignant biological properties of ovarian cancer by inducing apoptosis and autophagy via the inactivation of PI3K/AKT/mTOR pathway.

Tanshinone I (Tan-I) is one of the vital fatsoluble monomer components, which extracted from Chinese medicinal herb Salvia miltiorrhiza Bunge. It has been shown that Tan-I exhibited anti-tumour activities on different types of cancers. However, the underlying mechanisms by which Tan-Ⅰ regulates apoptosis and autophagy in ovarian cancer remain unclear. Thus, this study aimed to access the therapy effect of Tan-Ⅰ and the underlying mechanisms. Ovarian cancer cells A2780 and ID-8 were treated with different concentrations of Tan-Ⅰ (0, 1.2, 2.4, 4.8 and 9.6 μg/mL) for 24 hours. The cell proliferation was analysed by CCK8 assay, EdU staining and clone formation assay. Apoptosis was assessed by the TUNEL assay and flow cytometry. The protein levels of apoptosis protein (Caspase-3), autophagy protein (Beclin1, ATG7, p62 and LC3II/LC3I) and PI3K/AKT/mTOR pathway were determined by Western blot. Autophagic vacuoles in cells were observed with LC3 dyeing using confocal fluorescent microscopy. Anti-tumour activity of Tan-Ⅰ was accessed by subcutaneous xeno-transplanted tumour model of human ovarian cancer in nude mice. The Ki67, Caspase-3 level and apoptosis level were analysed by immunohistochemistry and TUNEL staining. Tan-Ⅰ inhibited the proliferation of ovarian cancer cells A2780 and ID-8 in a dose-dependent manner, based on CCK8 assay, EdU staining and clone formation assay. In additional, Tan-Ⅰ induced cancer cell apoptosis and autophagy in a dose-dependent manner in ovarian cancer cells by TUNEL assay, flow cytometry and Western blot. Tan-Ⅰ significantly inhibited tumour growth by inducing cell apoptosis and autophagy. Mechanistically, Tan-Ⅰ activated apoptosis-associated protein Caspase-3 cleavage to promote cell apoptosis and inhibited PI3K/AKT/mTOR pathway to induce autophagy. This is the first evidence that Tan-Ⅰ induced apoptosis and promoted autophagy via the inactivation of PI3K/AKT/mTOR pathway on ovarian cancer and further inhibited tumour growth, which might be considered as effective strategy.

Zhou J ，Jiang YY ，Chen H ，Wu YC ，Zhang L ... -  《-》

Tanshinone I induces apoptosis and pro-survival autophagy in gastric cancers.

Jing X ，Xu Y ，Cheng W ，Guo S ，Zou Y ，He L ... -  《-》

Honokiol inhibits in vitro and in vivo growth of oral squamous cell carcinoma through induction of apoptosis, cell cycle arrest and autophagy.

Honokiol, an active natural product derived from Magnolia officinalis, exerted anticancer effects through a variety of mechanisms on multiple types of cancers. In this study, the molecular mechanisms of honokiol in suppressing the human oral squamous cell carcinoma (OSCC) cells were evaluated. Treatment of two OSCC cell lines with honokiol resulted in reducing the cell proliferation and arresting the cell cycle at G1 stage which was correlated with the down-regulation of Cdk2 and Cdk4 and the up-regulation of cell cycle suppressors, p21 and p27. In addition, the caspase-dependent programmed cell death was substantially detected, and the autophagy was induced as the autophagosome formation and autophagic flux proceeded. Modulation of autophagy by autophagic inducer, rapamycin or inhibitors, 3-MA or bafilomycin, potentiated the honokiol-mediated anti-OSCC effects where honokiol exerted multiple actions in suppression of MAPK pathway and regulation of Akt/mTOR or AMPK pathways. As compared to clinical therapeutic agent, 5-FU, honokiol exhibited more potent activity against OSCC cells and synergistically enhanced the cytotoxic effect of 5-FU. Furthermore, orally administrated honokiol exerted effective antitumour activity in vivo in OSCC-xenografted mice. Thus, this study revealed that honokiol could be a promising candidate in preventing human OSCCs.

Huang KJ ，Kuo CH ，Chen SH ，Lin CY ，Lee YR ... -  《-》