Paclitaxel: new uses for an old drug

Zhang, Dongshan; Yang, Ruhao; Wang, S.; Dong, Zheng

doi:10.2147/dddt.s56801

Cited by 77 publications

(29 citation statements)

References 52 publications

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“…Pathological studies have indicated that VSMCs serve a key role in the development of PAH, and may therefore present a therapeutic target for PAH in the future. PTX is a commonly used anticancer drug with applications as chemotherapy drug in in breast cancer, ovarian cancer, head and neck cancer, esophageal cancer, lung cancer and others (26), applications in skin disorders, renal and hepatic fibrosis, inflammation, axon regeneration, limb salvage, and coronary artery restenosis (27). The effective therapeutic concentration of PTX ranges from 1 nmol/l to 100 µmol/l.…”

Section: Discussionmentioning

confidence: 99%

Effects of paclitaxel intervention on pulmonary vascular remodeling in rats with pulmonary hypertension

Zhao

Yang

et al. 2018

Exp Ther Med

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The aim of the present study was to investigate the effects of paclitaxel (PTX), at a non-cytotoxic concentration, on pulmonary vascular remodeling (PVR) in rats with pulmonary hypertension (PAH), and to explore the mechanisms underlying the PTX-mediated reversal of PVR in PAH. A total of 36 rats were divided into control group (n=12), model group (n=12) receiving a subcutaneous injection of monocrotaline (60 mg/kg) in the back on day 7 following left pneumonectomy and PTX group (n=12) with PTX (2 mg/kg) injection via the caudal vein 3 weeks following establishing the model. The degree of PVR among all groups, as well as the expression levels of Ki67, p27Kip1 and cyclin B1, were compared. The mean pulmonary artery pressure, right ventricular hypertrophy index [right ventricle/(left ventricle + septum) ratio] and the thickness of the pulmonary arterial tunica media in the model group were 58.34±2.01 mmHg, 0.64±0.046 and 65.3±3.3%, respectively, which were significantly higher when compared with 23.30±1.14 mmHg, 0.32±0.028 and 16.2±1.3% in the control group, respectively (P<0.01). The mean pulmonary artery pressure, right ventricular hypertrophy index and thickness of the pulmonary arterial tunica media in the PTX group were 42.35±1.53 mmHg, 0.44±0.029 and 40.5±2.6%, respectively, which were significantly lower when compared with the model group (P<0.01). Compared with the control group, the expression levels of Ki67 and cyclin B1 in the model group were significantly increased (P<0.01), while p27Kip1 expression was significantly reduced (P<0.01). Following PTX intervention, the expression levels of Ki67 and cyclin B1 were significantly reduced when compared with the model group (P<0.01), while p27Kip1 expression was significantly increased (P<0.01). The results of the present study suggest that PTX, administered at a non-cytotoxic concentration, may reduce PAH in rats, and prevent the effects of PVR in PAH. These effects of PTX may be associated with increased expression of p27Kip1 and decreased expression of cyclin B1.

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Section: Discussionmentioning

confidence: 99%

Effects of paclitaxel intervention on pulmonary vascular remodeling in rats with pulmonary hypertension

Zhao

Yang

et al. 2018

Exp Ther Med

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“…Goodness-of-fit test of SR, OLSR, PCR and PLSR models was performed to detect the best model for predicting each output variables (DW, intracellular paclitaxel, extracellular paclitaxel, total yield of paclitaxel and extracellular paclitaxel portion). High VAF, R 2 and RPD values and low RMSE and MAPE values displayed the model capability.…”

Section: Regression Modelsmentioning

confidence: 94%

“…Paclitaxel is a well-known chemotherapeutic agent widely applied as a therapy for various types of cancers [1], and this is also used as a treatment for non-cancerous human diseases [2]. Paclitaxel as a cytoskeletal drug arrests the proliferation of tumor cells following stabilizing the microtubules.…”

Section: Introductionmentioning

confidence: 99%

Whole fungal elicitors boost paclitaxel biosynthesis induction in Corylus avellana cell culture

et al. 2020

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Paclitaxel is an effective natural-source chemotherapeutic agent commonly applied to treat a vast range of cancers. In vitro Corylus avellana culture has been reported as a promising and inexpensive system for paclitaxel production. Fungal elicitors have been made known as the most efficient strategy for the biosynthesis induction of secondary metabolites in plant in vitro culture. In this research, C. avellana cell suspension culture (CSC) was exposed to cell extract (CE) and culture filtrate (CF) derived from Camarosporomyces flavigenus, either individually or combined treatment, in mid and late log phase. There is no report on the use of whole fungal elicitors (the combined treatment of CE and CF) for the elicitation of secondary metabolite biosynthesis in plant in vitro culture. The combined treatment of CE and CF significantly led to more paclitaxel biosynthesis and secretion than the individual use of them. Also, multivariate statistical approaches including stepwise regression (SR), ordinary least squares regression (OLSR), principal component regression (PCR) and partial least squares regression (PLSR) were used to model and predict paclitaxel biosynthesis and secretion. Based on value account for (VAF), root mean square error (RMSE), coefficient of determination (R 2), mean absolute percentage error (MAPE) and relative percent difference (RPD) can be concluded that mentioned regression models effectively worked only for modeling and predicting extracellular paclitaxel portion in C. avellana cell culture.

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“…Moreover, it is also used for the management of diseases such as head and neck cancers, smallcell and non-small-cell lung cancers (NSCLCs), and AIDS [36]. Apart from cancer, paclitaxel is also used in the treatment of coronary heart disease, inflammation, axon regeneration as well as degenerative brain diseases, renal and hepatic fibrosis [37]. Paclitaxel-bound liposomes were studied In vitro and In vivo and demonstrated to be effective in the treatment of pancreatic cancer [38].…”

Section: Resultsmentioning

confidence: 99%

Assessing the Specificity of Paclitaxel towards the Marker Proteins of Breast Cancer Using In silico Molecular Docking Study

Kumar

Kumar²,

Parthasarathy

2020

JPRI

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Breast cancer is highly prevalent next to lung cancer. Breast cancer occurs as a result of mutation in the genes like proto-oncogenes as well as tumor suppressor genes in a single clone of cells in the ductal and glandular regions of the breast. The drugs used to prevent breast cancer are Raloxifene hydrochloride and Tamoxifen citrate. The drugs used to treat breast cancer are Abemaciclib, Paclitaxel, Everolimus, Imatinib, Alpelisib, Anastrozole. Although several drug molecules had been developed, their specificity towards the potential breast cancer specific marker proteins such as activated threonine kinase 2/Protein kinase B (AKT2), cell division protein kinase 6 (CDK6), estrogen receptor (ER), human epidermal growth factor receptor type 2 (HER2), and poly ADP ribose polymerase1 (PARP1) need to be studied in silico. The present study was undertaken 1) to assess the specificity of paclitaxel towards the breast cancer specific marker proteins using molecular docking analysis and 2) to identify various physico-chemical properties of drug molecules including absorption, distribution, metabolism and excretion (ADME). The interaction between paclitaxel and the target proteins of breast cancer was analyzed using the Schrodinger Maestro Ver.2018.4. The results of the present study reveal that paclitaxel shows good binding interactions with the target proteins in the following order, ER > PARP1 > AKT2 >CDK6 > HER2. Among the five proteins, ER and PARP1 showed good binding interactions as compared to AKT2, CDK6 and HER2 proteins. The ADME properties of paclitaxel were predicted using QikProp module of Schrodinger Maestro version 2018.4. The present study warrant further studies which helps in the development of potent anticancer drug to treat breast cancer.

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Paclitaxel: new uses for an old drug

Cited by 77 publications

References 52 publications

Effects of paclitaxel intervention on pulmonary vascular remodeling in rats with pulmonary hypertension

Effects of paclitaxel intervention on pulmonary vascular remodeling in rats with pulmonary hypertension

Whole fungal elicitors boost paclitaxel biosynthesis induction in Corylus avellana cell culture

Assessing the Specificity of Paclitaxel towards the Marker Proteins of Breast Cancer Using In silico Molecular Docking Study

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