Amplified intracellular Ca2+ for synergistic anti-tumor therapy of microwave ablation and chemotherapy.

BACKGROUND: Developing new strategies to reduce the output power of microwave (MW) ablation while keeping anti-tumor effect are highly desirable for the simultaneous achievement of effective tumor killing and avoidance of complications. We find that mild MW irradiation can significantly increase intracellular Ca2+ concentration in the presence of doxorubicin hydrochloride (DOX) and thus induce massive tumor cell apoptosis. Herein, we designed a synergistic nanoplatform that not only amplifies the intracellular Ca2+ concentration and induce cell death under mild MW irradiation but also avoids the side effect of thermal ablation and chemotherapy. RESULTS: The as-made NaCl-DOX@PLGA nanoplatform selectively elevates the temperature of tumor tissue distributed with nanoparticles under low-output MW, which further prompts the release of DOX from the PLGA nanoparticles and tumor cellular uptake of DOX. More importantly, its synergistic effect not only combines thermal ablation and chemotherapy, but also obviously increases the intracellular Ca2+ concentration. Changes of Ca2+ broke the homeostasis of tumor cells, decreased the mitochondrial inner membrane potential and finally induced the cascade of apoptosis under nonlethal temperature. As such, the NaCl-DOX@PLGA efficiently suppressed the tumor cell progression in vivo and in vitro under mild MW irradiation for the triple synergic effect. CONCLUSIONS: This work provides a biocompatible and biodegradable nanoplatform with triple functions to realize the effective tumor killing in unlethal temperature. Those findings provide reliable solution to solve the bottleneck problem bothering clinics about the balance of thermal efficiency and normal tissue protection.

Total alkaloids of Tripterygium hypoglaucum (levl.) Hutch inhibits tumor growth both in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium hypoglaucum (levl.) Hutch (Celastraceae) (THH) root is a traditional Chinese medicinal herb commonly used for treating autoimmune diseases and cancer. Alkaloid is one of the most bioactive components of THH extract. To evaluate the in vitro and in vivo antitumor properties of the total alkaloids of THH (THHta). MATERIALS AND METHODS: THHta was extracted in pilot-scale. HCT116 cells were chose to establish human colon cancer xenograft model. The in vitro anti-tumor activity of THHta was tested by Cell malignant transformation test, Soft agar colony formation assay and MTT assay. The in vivo anti-tumor effect of THHta was confirmed by xenograft mouse model. THHta-induced apoptosis was examined by flow cytometry. The levels of apoptosis-related proteins were investigated by Western blot. RESULTS: TPA-induced cell transformation was significantly inhibited by THHta in JB6 Cl41 cells. THHta inhibits the growth of colon cancer cells in vitro in a significant dose-dependent manner. Compared to the control set, i.p. administration of THHta to xenograft mice significantly reduced both tumor weight and volume. Apoptosis induction of THHta was mediated by activation of caspase-3, PARP and inhibiting of Bcl-2, Bcl-xL and XIAP. CONCLUSION: THHta was effective in inhibiting tumor growth both in vitro and in vivo at less toxic concentrations by inducing apoptosis which suggested it could be developed as a potential anticancer agent.

[Vitexicarpin, a flavonoid from Vitex trifolia L., induces apoptosis in K562 cells via mitochondria-controlled apoptotic pathway].

AIM: To investigate the inhibitory effect of vitexicarpin on the proliferation of human cancer cells and its mechanism of action. METHODS: The inhibitory effect of vitexicarpin on the proliferation of human cancer cells was evaluated by the SRB method and its apoptosis-inducing effect was demonstrated by morphological observation under light microscope, flow cytometric analysis and agarose gel electrophoresis. The proteins related to apoptosis were examined by Western blotting analysis. RESULTS: Vitexicarpin significantly inhibited the proliferation of human cancer cells, A2780, HCT-15, HT-1080 and K562, with the IC50 values of (19.1 +/- 2.4) micromol x L(-1) for A2780(48 h), (0.66 +/- 0.10) micromol x L(-1) for HCT-15(48 h), (0.44 +/- 0.06) micromol x L(-1) for HT-1080 (48 h) and (0.28 +/- 0.14) micromol x L(-1) for K562 (24 h). The cells treated with vitexicarpin showed characteristic morphology typical for apoptosis and gave dose-dependent sub-G0/G1 peak in the flow cytometric analysis and DNA ladder on agarose gel electrophoresis. In Western blotting analysis, the cleavage of PARP and caspase-3, the release of cytochrome c from mitochondria into the cytosol, the decrease of Bcl-2 expression level, and the down-regulation of the ratio of Bcl-2/Bax expression level were examined in the K562 cells treated with vitexicarpin. CONCLUSION: Vitexicarpin induces apoptosis in K562 cells via mitochondria-controlled apoptotic pathway.

[Apoptosis-inducing activity of extract from Chinese herb, Albizzia Lucidior I. Nielsen].

BACKGROUND & OBJECTIVE: Chinese herb Albizzia Lucidior I. Nielsen (ALN) belongs to Albizzia of Legume. It was reported that the chemical constituents from the bark of Albizza plants possess antitumor activity. So far there was no report about the components of Albizzia Lucidior I. Nielsen and its bioactivities. This study was designed to investigate the apoptosis-inducing activity of ALN extract on human tumor cells and the related mechanism. METHODS: The effect of ALN extract on tumor cells proliferation, cell cycle distribution, and apoptosis inducing were determined by cell molecular biological methods including MTT assay, nucleus morphological characteristics observation, cell size examination, agarose gel electrophoresis, and flow cytometry. Living cells reaction to ALN extract was also detected by cytosensor microphysiometry. Apoptosis related proteins, poly(ADP-ribose) polymersase (PARP), bcl-2 and Bax protein levels were measured by Western blot. RESULTS: ALN extract showed proliferation inhibition on human tumor cells by inducing apoptosis. The IC50 value to K562 cell line was (29.04 +/- 12.67) micrograms/ml. Western blot analysis showed that PARP was proteolysized and Bax protein level was enhanced, whereas bcl-2 protein level was unchanged. CONCLUSIONS: ALN extract induce human tumor cells apoptosis, probably by increasing Bax protein expression.