Effects of jasplakinolide on cytotoxicity, cytoskeleton and apoptosis in two different colon cancer cell lines treated with m-THPC-PDT.

Colorectal cancer (CRC) is a common malignant tumor, and metastasis is one of the most important challenges in the treatment of CRC. Photodynamic therapy (PDT) is a novel and non-invasive treatment that influence cytoskeleton and to reduce cancer metastases. In addition, cytoskeleton is related to cancer metastases. Two isogenic colorectal cancer cell lines SW480 and SW620 were used in the present study, we found that m-THPC mediated PDT changed the cytotoxicity, apoptosis and cytoskeleton in both cell lines. Interestingly, the expression of intermediate filaments protein cytokeratin18 were different in the two cell lines. In order to further confirm the relationship between cytoskeleton and cell migration, we combined with microfilament stabilizer jasplakinolide (JASP) to observe the effects of microfilaments on cell migration, cytotoxicity and apoptosis. Taken together, these findings suggest that m-THPC-PDT could induce cytoplasmic cytoskeleton destruction in both types of cells, especially on microfilaments and microtubules. Moreover, in SW480 cells, microtubules may participate in the apoptosis process induced by m-THPC-PDT, while microfilaments may participate in the process of m-THPC-PDT inhibiting cell migration. But in SW620 cells, only microfilaments may be involved in m-THPC-PDT induced apoptosis and inhibition of cell migration.

Effects of meta-tetrahydroxyphenylchlorin photodynamic therapy on isogenic colorectal cancer SW480 and SW620 cells with different metastatic potentials.

The aim of this study is to investigate the antitumor effects and possible mechanisms of meta-tetrahydroxyphenylchlorin-mediated photodynamic therapy (m-THPC-PDT) on human primary (SW480) and metastatic (SW620) colon cancer cell lines. SW480 and SW620 cells were incubated with various concentrations of m-THPC, followed by photodynamic irradiation. Subcellular localization of m-THPC in cells was observed with confocal laser scanning microscopy (CLSM). Photocytotoxicity of m-THPC in the two cells was investigated by using MTT assay. The flow cytometry was employed to detect the cell apoptosis. The migration and long-term recovery ability were determined by scratch test and colony formation assay respectively. CLSM showed that m-THPC was mainly distributed within the endoplasmic reticulum (ER) and lysosome of SW480 cells and within the lysosome and mitochondria of SW620 cells. m-THPC-PDT induced a dose-dependent and light energy-dependent cytotoxicity in SW480 and SW620 cells. Apoptosis rate was approximately 65 and 25% in SW480 and SW620 respectively when the concentration of m-THPC increased to 11.76 µM. However, the rate of necrotic cells had no significant changes in two cell lines. The colony formation and migration ability of the two cell lines were decreased with m-THPC-PDT treatment in a dose-dependent manner. PDT with m-THPC not only could effectively inhibit cell proliferation and decrease migration ability and colony formation ability, but also could effectively kill SW480 and SW620 cells in a dose-dependent manner in vitro. These results suggest that m-THPC is a promising sensitizer that warrants further development and extensive studies towards clinical use of colorectal cancer.