1.Research progress on the source, production, and anti-cancer mechanisms of paclitaxel.
Yan-Hua YANG ; Jia-Wang MAO ; Xiao-Li TAN
Chinese Journal of Natural Medicines (English Ed.) 2020;18(12):890-897
Paclitaxel, a tetracyclic diterpenoid compounds, was firstly isolated from the bark of the Pacific yew trees. Currently, as a low toxicity, high efficiency, and broad-spectrum natural anti-cancer drug, paclitaxel has been widely used against ovarian cancer, breast cancer, uterine cancer, and other cancers. As the matter of fact, natural paclitaxel from Taxus species has been proved to be environmentally unsustainable and economically unfeasible. For this reason, researchers from all over the world are devoted to searching for new ways of obtaining paclitaxel. At present, other methods, including artificial cultivation of Taxus plants, microbial fermentation, chemical synthesis, tissue and cell culture have been sought and developed subsequently. Meanwhile, the biosynthesis of paclitaxel is also an extremely attractive method. Unlike other anti-cancer drugs, paclitaxel has its unique anti-cancer mechanisms. Here, the source, production, and anti-cancer mechanisms of paclitaxel were summarized and reviewed, which can provide theoretical basis and reference for further research on the production, anti-cancer mechanisms and utilization of paclitaxel.
Antineoplastic Agents, Phytogenic/pharmacology*
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Humans
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Neoplasms/drug therapy*
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Paclitaxel/pharmacology*
2.Optimization of formulation of paclitaxel nanosuspension encapsulated by erythrocyte membrane based on Box-Behnken method.
Yue-Yue FAN ; Yue-Xin CUI ; Wen-Yan HAO ; Meng-Yu CHEN ; Yang YANG ; Chun-Sheng GAO
China Journal of Chinese Materia Medica 2022;47(9):2457-2464
In view of the longevity and innate immune escape of red blood cells, this study designed the red blood cell membrane-coated paclitaxel nanosuspension [RBC-(PTX)NS] and investigated its physicochemical properties and antitumor effect in vitro. Paclitaxel nanosuspension [(PTX)NS] was prepared by ultrasonic precipitation and then RBC-(PTX)NS by ultrasonic coating. The formulation of(PTX)NS was optimized with Box-Behnken method and indexes of particle diameter, zeta potential, and stability. The morphology, particle diameter, stability, in vitro dissolution, and antitumor effect of(PTX)NS and RBC-(PTX)NS were characterized. The results showed that the particle diameter and zeta potential were(129.38±0.92) nm and(-22.41±0.48) mV, respectively, for the optimized(PTX)NS, while(142.5±0.68) nm and(-29.85±0.53) mV, respectively, for RBC-(PTX)NS. Under the transmission electron microscope,(PTX)NS was spherical and RBC-(PTX)NS had obvious core-shell structure. RBC-(PTX)NS remained stable for 5 days at 4 ℃. The in vitro dissolution test demonstrated that the cumulative release rate of RBC-(PTX)NS reached 79% within 20 min, which was significantly higher than that(25%) of(PTX)NS(P<0.05). As evidenced by MTT assay, RBC-(PTX)NS highly inhibited the proliferation of HepG2 cells in a dose-dependent manner. The cell membrane-coated nano-preparation preparation method is simple and reproducible. It improves the solubility of PTX and endows RBC-(PTX)NS with higher stability and stronger cytotoxicity. Thus, it is a new method for the delivery of PTX via nanocrystallization.
Erythrocyte Membrane
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Nanoparticles/chemistry*
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Paclitaxel/pharmacology*
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Particle Size
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Suspensions
3.Effects of paclitaxel loaded ultrasound contrast agents on cell cycles and ultrastructural features of HepG2 cells.
Yao LIU ; Juan KANG ; Xiao-ling WU ; Zhi-gang WANG ; Zhao-xia WANG ; Pan LI
Chinese Journal of Hepatology 2008;16(5):360-362
OBJECTIVESTo investigate the effects of paclitaxel loaded ultrasound contrast agents on cell cycles and ultrastructural features of HepG2 cells.
METHODSHepG2 cells were cultured, and divided into a blank control group, a paclitaxel group, an ultrasound contrast agents group, and a paclitaxel loaded ultrasound contrast agents group. Cell cycles of the four groups were detected by flow cytometry, and the ultrastructural changes of the cells were observed under a transmission electron microscope.
RESULTSPaclitaxel loaded ultrasound contrast agents blocked the HepG2 cells at their G2/M phases, and it also induced more apoptosis of the HepG2 cells.
CONCLUSIONSPaclitaxel loaded ultrasound contrast agents can block HepG2 cells at the G2/M phase and induce apoptosis of the cells.
Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Contrast Media ; pharmacology ; Hep G2 Cells ; Humans ; Microscopy, Electron, Transmission ; Paclitaxel ; pharmacology
4.Inhibitory effect of photodynamic therapy combined with paclitaxel on the proliferation of esophageal carcinoma Eca-109 cells.
Zhi-feng ZHANG ; Yi HUANG ; Xi SHI ; Ri-xiong WANG ; Xiao-yan LIN ; Xue-de LIN ; Hang ZHENG ; Li-bo LI
Journal of Southern Medical University 2010;30(6):1310-1315
OBJECTIVETo investigate the inhibitory effect of photodynamic therapy (PDT) in combination with paclitaxel (PCT) on proliferation in esophageal carcinoma Eca-109 cells line.
METHODSEca-109 cells were treated with PCT alone, HPD alone at different doses, or their combinations. For the combined treatments, the cells were exposed to PCT for 12 h followed by incubation with HPD at high, middle or low concentrations for 4 h. PDT was then performed on these treated cells and fluorescence microscopic observation was made before and after PDT. The cell survival was measured by MTT assay, and the cell apoptosis rate analyzed by flow cytometry after a 24-h cell incubation following PDT.
RESULTSThe fluorescence excitation of the cells was weakened after PDT. Combined treatments resulted in significantly lowered cell survival rate and increased cell apoptosis rates as compared to those of the control cells and the cells treated with PCT alone and low-dose HPD (P<0.01). Significant differences were also noted among the cells exposed to HPD at different concentrations (P<0.05).
CONCLUSIONPDT combined with PCT have significant synergetic effects in inhibiting the proliferation of human esophageal carcinoma cells and inducing their apoptosis in vitro.
Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Esophageal Neoplasms ; pathology ; Humans ; Paclitaxel ; pharmacology ; Photochemotherapy
5.Targeted killing of CD133+ lung cancer stem cells using paclitaxel-loaded PLGA-PEG nanoparticles with CD133 aptamers.
Li Ying PANG ; Xiao Long HUANG ; Ling Ling ZHU ; Han Yan XIAO ; Meng Yu LI ; Hui Lin GUAN ; Jie GAO ; Hong JIN
Journal of Southern Medical University 2022;42(1):26-35
OBJECTIVE:
To construct a polylactic acid-glycolic acid-polyethylene glycol (PLGA-PEG) nanocarrier (N-Pac-CD133) coupled with a CD133 nucleic acid aptamer carrying paclitaxel for eliminating lung cancer stem cells (CSCs).
METHODS:
Paclitaxel-loaded N-Pac-CD133 was prepared using the emulsion/solvent evaporation method and characterized. CD133+ lung CSCs were separated by magnetic bead separation and identified for their biological behaviors and gene expression profile. The efficiency of paclitaxel-loaded N-Pac-CD133 for targeted killing of lung cancer cells was assessed in vitro. SCID mice were inoculated with A549 cells and received injections of normal saline, empty nanocarrier linked with CD133 aptamer (N-CD133), paclitaxel, paclitaxel-loaded nanocarrier (N-Pac) or paclitaxel-loaded N-Pac-CD133 (n=8, 5 mg/kg paclitaxel) on days 10, 15 and 20, and the tumor weight and body weight of the mice were measured on day 40.
RESULTS:
Paclitaxel-loaded N-Pac-CD133 showed a particle size of about 100 nm with a high encapsulation efficiency (>80%) and drug loading rate (>8%), and was capable of sustained drug release within 48 h. The CD133+ cell population in lung cancer cells showed the characteristic features of lung CSCs, including faster growth rate (30 days, P=0.001) and high expressions of tumor stem cell markers OV6(P < 0.001), CD133 (P=0.001), OCT3/4 (P=0.002), EpCAM (P=0.04), NANOG (P=0.005) and CD44 (P=0.02). Compared with N-Pac and free paclitaxel, paclitaxel-loaded N-Pac-CD133 showed significantly enhanced targeting ability and cytotoxicity against lung CSCs in vitro (P < 0.001) and significantly reduced the formation of tumor spheres (P < 0.001). In the tumor-bearing mice, paclitaxel-loaded N-Pac-CD133 showed the strongest effects in reducing the tumor mass among all the treatments (P < 0.001).
CONCLUSION
CD133 aptamer can promote targeted delivery of paclitaxel to allow targeted killing of CD133+ lung CSCs. N-Pac-CD133 loaded with paclitaxel may provide an effective treatment for lung cancer by targeting the lung cancer stem cells.
Animals
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Cell Line, Tumor
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Drug Carriers
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Lung
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Mice
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Mice, SCID
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Nanoparticles
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Neoplasms
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Neoplastic Stem Cells
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Paclitaxel/pharmacology*
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Polyethylene Glycols/pharmacology*
6.Biological characteristics of microtubule and related drug research.
Jian-nong LI ; Jian-dong JIANG
Acta Pharmaceutica Sinica 2003;38(4):311-315
Amino Acids
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isolation & purification
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Animals
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Antineoplastic Agents, Phytogenic
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pharmacology
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Binding Sites
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Colchicine
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pharmacology
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Humans
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Microtubules
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drug effects
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physiology
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Paclitaxel
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pharmacology
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Tubulin
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chemistry
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isolation & purification
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metabolism
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Vinblastine
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pharmacology
7.Effects of gathering season and three age affect on main active components of Taxus madia.
Xiaojuan SHI ; Zhiming XU ; Shunhua FU ; Xinfeng ZHANG ; Zhaobin HE ; Hongliang DU
China Journal of Chinese Materia Medica 2010;35(19):2538-2540
OBJECTIVETo reveal the influence of harvest season and tree age on the content of taxol and 10-DAB III, and provide the basis for the harvest time of Taxus madia.
METHODBranches and leaves of the labeled 25 three-year-old plants and 25 five-year-old plants were collected every two months from March 26,2009 to January 26, 2010. Taxol and 10-DAB III content of different age and growth season of Taxus in branches were determined by HPLC.
RESULTTaxol and 10-DAB III content were significantly different in different harvesting age. The content of five-year-old plants was significantly higher than that of three-year-old plants. Taxol and 10-DAB III contents were significantly different in different harvesting season, and the highest content of taxol and 10-DAB III was 0.56, 0.32 mg x g(-1), respectively, in May.
CONCLUSIONThe May is the suitable harvest season for T. madia, but the suitable harvest age need further study which according to the main active component and biomass accumulation.
Antineoplastic Agents, Phytogenic ; analysis ; pharmacology ; Asteraceae ; chemistry ; Chromatography, High Pressure Liquid ; Paclitaxel ; analysis ; pharmacology ; Plant Preparations ; pharmacology ; Seasons ; Taxoids ; analysis ; pharmacology ; Taxus ; chemistry ; drug effects ; Trees ; chemistry
8.Combination of Se-methylselenocysteine, D-α-tocopheryl succinate, β-carotene, and L-lysine can prevent cancer metastases using as an adjuvant therapy.
Yunlong CHENG ; Shu LIAN ; Shuhui LI ; Yusheng LU ; Jie WANG ; Xiaoxiao DENG ; Shengyi ZHAI ; Lee JIA
Journal of Zhejiang University. Science. B 2022;23(11):943-956
OBJECTIVES:
Primary tumor treatment through surgical resection and adjuvant therapy has been extensively studied, but there is a lack of effective strategies and drugs for the treatment of tumor metastases. Here, we describe a functional product based on a combination of compounds, which can be used as an adjuvant therapy and has well-known mechanisms for inhibiting cancer metastases, improving anti-cancer treatment, and enhancing immunity and antioxidant capacity. Our designed combination, named MVBL, consists of four inexpensive compounds: L-selenium-methylselenocysteine (MSC), D-α-tocopheryl succinic acid (VES), β-carotene (β-Ca), and L-lysine (Lys).
METHODS:
The effects of MVBL on cell viability, cell cycle, cell apoptosis, cell migration, cell invasion, reactive oxygen species (ROS), and paclitaxel (PTX)-combined treatment were studied in vitro. The inhibition of tumor metastasis, antioxidation, and immune enhancement capacity of MVBL were determined in vivo.
RESULTS:
MVBL exhibited higher toxicity to tumor cells than to normal cells. It did not significantly affect the cell cycle of cancer cells, but increased their apoptosis. Wound healing, adhesion, and transwell assays showed that MVBL significantly inhibited tumor cell migration, adhesion, and invasion. MVBL sensitized MDA-MB-231 breast cancer cells to PTX, indicating that it can be used as an adjuvant to enhance the therapeutic effect of chemotherapy drugs. In mice, experimental data showed that MVBL inhibited tumor metastasis, prolonged their survival time, and enhanced their antioxidant capacity and immune function.
CONCLUSIONS
This study revealed the roles of MVBL in improving immunity and antioxidation, preventing tumor growth, and inhibiting metastasis in vitro and in vivo. MVBL may be used as an adjuvant drug in cancer therapy for improving the survival and quality of life of cancer patients.
Mice
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Animals
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beta Carotene
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Lysine/pharmacology*
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Antioxidants/pharmacology*
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Quality of Life
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Paclitaxel/pharmacology*
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Apoptosis
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alpha-Tocopherol
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Succinates/pharmacology*
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Cell Line, Tumor
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Cell Proliferation
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Neoplasms
9.Inhibitory effect of 17-AAG combined with paclitaxel on proliferation of esophageal squamous cell carcinoma Eca-109 cells in vitro.
Size CHEN ; Xuemei CHEN ; Yuqi LI ; Shu YANG ; Xianyi MO ; Fan ZHANG ; Kailan MO ; Ying DING
Journal of Southern Medical University 2015;35(6):844-847
OBJECTIVETo investigate the effect of 17-AAG combined with paclitaxel (PTX) on the proliferation and apoptosis of esophageal squamous cell carcinoma cell line Eca-109 in vitro.
METHODSEca-109 cells were treated with 17-AAG and PTX either alone or in combination. The proliferation of Eca-109 cells was detected by MTT assay, and the cell cycle changes and cell apoptosis were determined by flow cytometry.
RESULTSCompared with the control group, both 17-AAG and PTX significantly inhibited the proliferation of Eca-109 cells. A combined treatment of the cells with 0.5 µmol/L PTX and 0.625 µmol/L 17-AAG produced an obviously stronger inhibitory effect on the cell proliferation than either of the agents used alone (P<0.01). Flow cytometry showed that, 17-AAG and PTX used alone caused Eca-109 cell cycle arrest in G2/M phase and S phase, respectively, and their combined use caused cell cycle arrest in both G2/M and S phases. The cell apoptosis rates of Eca-109 cells treated with 17-AAG, PTX and their combination were 4.52%, 10.91%, and 29.88%, respectively, all significantly higher than that in the control group (1.32%); the combined treatment resulted in a distinct apoptotic peak that was significantly higher than that caused by either of the agents alone.
CONCLUSION17-AAG and PTX can inhibit cell proliferation and promote apoptosis of Eca-109 cells, and their combination produces stronger effects in inhibiting cell proliferation and increasing cell apoptosis.
Apoptosis ; Benzoquinones ; pharmacology ; Carcinoma, Squamous Cell ; pathology ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Esophageal Neoplasms ; pathology ; Humans ; Lactams, Macrocyclic ; pharmacology ; Paclitaxel ; pharmacology
10.Influence of SNCG transfection on the effectiveness of anti-tumor drugs in PC-3 cell lines.
Jia-Liang CHEN ; Bo WANG ; Li-Rong ZHANG ; Bang-Shun HE ; Yu-Qin PAN ; Qing-Di ZENG ; Hua-Xin JIANG ; Shu-Kui WANG
National Journal of Andrology 2008;14(12):1077-1082
OBJECTIVETo observe the sensitivity of the PC-3 cell lines transfected with the PCI-NEO-SNCG plasmid to Cisplatin (DDP), 5-Fluorouracil (5-FU), Adriamycin (ADM), Vincristine (VCR) and Paclitaxel (TAX), and to explore the influence of the SNCG expression on the effectiveness of anti-tumor drugs.
METHODSThe plasmids PCI-NEO and PCI-NEO-SNCG were transfected into the hormone-independent prostate cancer cell lines PC-3. RT-PCR was adopted to examine the expression of SNCG in the PC-3 cell lines. The MTT method was employed to detect the suppressive effects of different anti-tumor drugs (DDP, ADM, 5-FU, VCR and TAX) on the cell lines transfected with PCI-NEO and PCI-NEO-SNCG. Flow cytometry was used to analyze the cell cycles and apoptosis of the transfected cells treated with TAX.
RESULTSThe 5 anti-tumor drugs suppressed the growth of the cell lines transfected with the plasmids PCI-NEO and PCI-NEO-SNCG in a time-dependant manner. The comparison between the growth-suppressing effects of different anti-tumor drugs on the PC-3 cell lines showed no significant differences between the group transfected with PCI-NEO and that with PCI-NEO-SNCG in DDP, 5-FU, ADM and VCR (P > 0.05), while the rate of suppression of TAX on the latter cell lines was significantly lower than that on the former (P < 0.01). Compared with the PCI-NEO-SNCG plasmid transfected cell lines, after treated with TAX for 48 hours, those transfected with the PCI-NEO plasmid exhibited a significantly larger proportion of cells remaining in the G2-M stage (P < 0.01), a smaller proportion in the G0-G1 and S stages (P < 0.01) and a significantly higher expression of Caspase-3 (P < 0.01).
CONCLUSIONThe significant reduction of the growth-suppressing effect of TAX in the SNCG-transfected PC-3 cell lines suggests that the expression of SNCG may restrain the effect of TAX. These findings have provided evidence and guide to the individual chemotherapy of prostate cancer.
Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; genetics ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Drug Screening Assays, Antitumor ; Humans ; Male ; Neoplasm Proteins ; genetics ; Paclitaxel ; pharmacology ; Prostatic Neoplasms ; Transfection ; gamma-Synuclein ; genetics