1.Phosphorylation of Cofilin-1 Enhances Paclitaxel Resistance of Epithelial Ovarian Cancer Cells by Inhibiting Apoptosis.
Min LI ; Xu Dong DONG ; Qiu Bo LYU ; Wei ZHANG ; Shuai HUANG ; Chun Xue YANG ; Di CUI ; Hui Ying LAI
Biomedical and Environmental Sciences 2021;34(6):465-477
Objective:
To investigate the molecular mechanism of high phosphorylation levels of cofilin-1 (p-CFL-1) associated with paclitaxel resistance in epithelial ovarian cancer (EOC) cells.
Methods:
Cells displaying varying levels of p-CFL-1 and CFL-1 were created by plasmid transfection and shRNA interference. Cell inhibition rate indicating paclitaxel efficacy was assessed by Cell Counting Kit-8 (CCK-8) assay. Apoptosis was assessed by flow cytometry and protein levels were detected by western blotting. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression levels of phosphokinases and phosphatases of CFL-1. Survival analysis evaluated the correlation between the prognosis of EOC patients and the levels of p-CFL-1 and slingshot-1 (SSH-1).
Results:
High levels of p-CFL-1 were observed in EOC cells that survived treatment with high doses of paclitaxel. SKOV3 cell mutants with upregulated p-CFL-1 showed impaired paclitaxel efficacy, as well as decreased apoptosis rates and pro-survival patterns of apoptosis-specific protein expression. Cytoplasmic accumulation of p-CFL-1 inhibited paclitaxel-induced mitochondrial apoptosis. SSH-1 silencing mediated CFL-1 phosphorylation in paclitaxel-resistant SKOV3 cells. Clinically, the high level of p-CFL-1 and the low level of SSH-1 in EOC tissues were closely related to chemotherapy resistance and poor prognosis in EOC patients.
Conclusion
The SSH-1/p-CFL-1 signaling pathway mediates paclitaxel resistance by apoptosis inhibition in EOC and is expected to be a potential prognostic predictor.
Antineoplastic Agents, Phytogenic/therapeutic use*
;
Apoptosis
;
Carcinoma, Ovarian Epithelial/metabolism*
;
Cell Line, Tumor
;
Cofilin 1/metabolism*
;
Drug Resistance, Neoplasm
;
Female
;
Humans
;
Ovarian Neoplasms/metabolism*
;
Paclitaxel/therapeutic use*
;
Phosphoprotein Phosphatases/metabolism*
;
Phosphorylation
2.Analysis and monitoring of traditional Chinese medicines for tumor based on data mining.
Xiao-Xia WANG ; Yuan-Yuan HAN ; Gui-Ying SHI ; Li-Mei HU ; Ping LU ; Fang LIU
China Journal of Chinese Materia Medica 2020;45(2):444-450
The traditional Chinese medicine(TCM) decoction pieces for treating tumors in China-Japan Friendship Hospital in both outpatient and inpatient departments from January 1 to December 31, 2018 were analyzed in this paper, and the statistical analysis on the frequency and proportion of TCM decoction pieces, as well as the average dosage and dosage range were conducted. Such data were then compared with Chinese Pharmacopoeia. At the same time, data mining association rules were used to study the compatibility of TCM in oncology, and finally, the drug use in TCM was discussed. The top 20(use frequency) TCM decoction pieces for tumors were mainly based on tonic medicines; the use frequency of toxic TCM decoction pieces was low, mainly of small poisonous pieces, with dosage exceeding pharmacopoeia. The drug combinations with higher frequency included Fried Atractylodis Macrocephalae Rhizoma-Poria Cocos(16.11%), and Astragali Radix-Poria Cocos(15.10%). Drug pairs with strong associations included Achyranthes Bidentata→Parasitic Loranthus, Coix Seed→Achyranthes Bidentata, Achyranthes Bidentata→Hairyvein Agrimony, Cuscutae Semen→Achyranthes Bidentata and so on. According to the use of drugs, the drug monitoring can be emphasized from the aspects of usage and dosage, selection of processed TCM, compatibility, decoction methods, and patient education. Pharmacists can analyze the characteristics and regularity of the use of TCM for tumors through data mining methods, and this can be a cutting point for drug monitoring.
Antineoplastic Agents, Phytogenic/therapeutic use*
;
China
;
Data Mining
;
Drugs, Chinese Herbal/therapeutic use*
;
Humans
;
Japan
;
Medicine, Chinese Traditional
;
Neoplasms/drug therapy*
3.Anti-cancer activities of S-allylmercaptocysteine from aged garlic.
Yi LV ; Kwok-Fai SO ; Nai-Kei WONG ; Jia XIAO
Chinese Journal of Natural Medicines (English Ed.) 2019;17(1):43-49
While most types of malignancies remain recalcitrant to treatment, application of natural products or their analogs in daily life has offered some hopes as an effective prophylaxis against cancer onset and progression in the past decades. Emerging evidence supports a link between garlic consumption and decreased cancer incidence. Notably, aged garlic extract (AGE) exhibits stronger anti-cancer activities than that of fresh garlic, by virtue of enrichment of several AGE-specific organosulfur compounds, including S-allylmercaptocysteine (SAMC). In this review, we summarize the up-to-date mechanistic pathways associated with the anti-proliferative, anti-metastatic and pro-apoptotic effects of SAMC in various cancer models. Based upon the proven safety and improved understanding on its anti-neoplastic properties, SAMC has gained recognition as a promising daily food supplement for cancer prevention or management.
Animals
;
Antineoplastic Agents, Phytogenic
;
chemistry
;
pharmacology
;
therapeutic use
;
Apoptosis
;
drug effects
;
Cysteine
;
analogs & derivatives
;
chemistry
;
pharmacology
;
therapeutic use
;
Disease Models, Animal
;
Garlic
;
chemistry
;
Humans
;
Molecular Structure
;
Neoplasms
;
drug therapy
;
metabolism
;
Signal Transduction
;
drug effects
4.Impact of taxanes on androgen receptor signaling.
Shanshan BAI ; Bryan Y ZHANG ; Yan DONG
Asian Journal of Andrology 2019;21(3):249-252
The development and progression of metastatic castration-resistant prostate cancer is the major challenge in the treatment of advanced prostate cancer. The androgen receptor signaling pathway remains active in metastatic castration-resistant prostate cancer. Docetaxel and cabazitaxel are the first- and second-line chemotherapy, respectively, for patients with metastatic castration-resistant prostate cancer. These two taxanes, in general, function by (i) inhibiting mitosis and inducing apoptosis and (ii) preventing microtubule-dependent cargo trafficking. In prostate cancer, taxanes have been reported to inhibit the nuclear translocation and activity of the androgen receptor. However, whether this is attainable or not clinically remains controversial. In this review, we will provide a comprehensive view of the effects of taxanes on androgen receptor signaling in prostate cancer.
Antineoplastic Agents, Phytogenic/therapeutic use*
;
Humans
;
Male
;
Prostatic Neoplasms, Castration-Resistant/drug therapy*
;
Receptors, Androgen/drug effects*
;
Signal Transduction/drug effects*
;
Taxoids/therapeutic use*
5.Clinical observation of Shuanghuang Shengbai Granule () on prevention and treatment of myelosuppression caused by chemotherapy in cancer patients.
Li-Fang WANG ; Zhen-Ye XU ; Zhong-Qi WANG ; Ming ZHANG ; Gui-Ying YAN ; An-Ji HOU ; Hai-Bin DENG ; Ji WU ; Xiao-Zhen ZHAO ; Yi XIANG ; Lei YU
Chinese journal of integrative medicine 2017;23(2):105-109
OBJECTIVETo study the efficacy and safety of Shuanghuang Shengbai Granule (, SSG), a traditional Chinese herbal medicine, on myelosuppression of cancer patients caused by chemotherapy.
METHODSA total of 330 patients were randomly assigned to the treatment group (220 cases, analysed 209 cases) and the control group (110 cases, analysed 102 cases) with a 2:1 ratio by envelope method. The patients in the treatment group at the first day of chemotherapy started to take SSG for 14 days, while the patients in the control group took Leucogon Tablets. The changes of the blood routine, clinical symptoms and immune function in both groups were observed for safety and efficacy evaluation.
RESULTSAt the 7th day of chemotherapy, the white blood cells (WBCs) level in the treatment group was significantly higher than that in the control group (P<0.05). After treatment, the WBCs rate in the normal range accounted for 50.2% in the treatment group, the myelosuppression of WBCs and neutrophil were mainly grade I, while 8.1% and 5.7% of patients emerged grade III and grade IV myelosuppression, respectively. The incidence of myelosuppression of the treatment group was significantly lower than that of the control group (P<0.05). The total effective rate of Chinese medicine syndrome in the treatment group was significantly higher than that in the control group (84.2% vs. 72.5%, P<0.05). The immune cell levels in both groups were maintained in the normal range. Compared with that before treatment, the levels of CD3and CD4cells were significantly increased in the treatment group after treatment (P<0.05). The discrepancy of CD3and CD4cell activity before and after treatment in both groups were significantly different (P<0.05). No obvious adverse event occurred in both groups.
CONCLUSIONSSG had a protection effect on bone marrow suppression, and alleviated the clinical symptoms together with clinical safety.
Antineoplastic Agents, Phytogenic ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Granulocyte Precursor Cells ; drug effects ; Humans ; Immune Tolerance ; drug effects ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Neoplasms ; drug therapy ; Pancytopenia ; chemically induced ; prevention & control ; Treatment Outcome
6.Research of Brucea javanica against cancer.
Zheng YAN ; Gui-Fang GUO ; Bei ZHANG
Chinese journal of integrative medicine 2017;23(2):153-160
Brucea javanica, a Chinese herbal medicine, combined with conventional anticancer modalities, has been widely used for treatment of various cancers. Based on researches over the last decades, authors briefly summarized its active constituents, molecular mechanisms and clinical application for cancer treatment.
Antineoplastic Agents, Phytogenic
;
therapeutic use
;
Apoptosis
;
drug effects
;
Biomedical Research
;
methods
;
trends
;
Brucea
;
chemistry
;
Drugs, Chinese Herbal
;
therapeutic use
;
Humans
;
Neoplasms
;
drug therapy
;
pathology
;
Phytotherapy
7.Anti-tumor activity of wogonin, an extract from Scutellaria baicalensis, through regulating different signaling pathways.
Do Luong HUYNH ; Neelesh SHARMA ; Amit KUMAR SINGH ; Simrinder SINGH SODHI ; Jiao-Jiao ZHANG ; Raj Kumar MONGRE ; Mrinmoy GHOSH ; Nameun KIM ; Yang HO PARK ; Dong KEE JEONG
Chinese Journal of Natural Medicines (English Ed.) 2017;15(1):15-40
Wogonin is a plant flavonoid compound extracted from Scutellaria baicalensis (Huang-Qin or Chinese skullcap) and has been studied thoroughly by many researchers till date for its anti-viral, anti-oxidant, anti-cancerous and neuro-protective properties. Numerous experiments conducted in vitro and in vivo have demonstrated wogonin's excellent tumor inhibitory properties. The anti-cancer mechanism of wogonin has been ascribed to modulation of various cell signaling pathways, including serine-threonine kinase Akt (also known as protein kinase B) and AMP-activated protein kinase (AMPK) pathways, p53-dependent/independent apoptosis, and inhibition of telomerase activity. Furthermore, wogonin also decreases DNA adduct formation with a carcinogenic compound 2-Aminofluorene and inhibits growth of drug resistant malignant cells and their migration and metastasis, without any side effects. Recently, newly synthesized wogonin derivatives have been developed with impressive anti-tumor activity. This review is the succinct appraisal of the pertinent articles on the mechanisms of anti-tumor properties of wogonin. We also summarize the potential of wogonin and its derivatives used alone or as an adjunct therapy for cancer treatment. Furthermore, pharmacokinetics and side effects of wogonin and its analogues have also been discussed.
Animals
;
Antineoplastic Agents, Phytogenic
;
pharmacology
;
therapeutic use
;
DNA Adducts
;
metabolism
;
Drug Resistance, Neoplasm
;
drug effects
;
Drugs, Chinese Herbal
;
pharmacology
;
therapeutic use
;
Flavanones
;
pharmacology
;
therapeutic use
;
Humans
;
Neoplasms
;
drug therapy
;
metabolism
;
Phytotherapy
;
Scutellaria baicalensis
;
chemistry
;
Signal Transduction
;
drug effects
8.Anti-prostate cancer effect of roemerine: An experimental study.
Hong-Bin MA ; Zhong-Shi TIAN ; Shi-Liang GUI ; Wei-Guo CUI ; Wei LI
National Journal of Andrology 2017;23(1):27-33
Objective:
To investigate the anti-prostate cancer (PCa) effect of roemerine in vitro and in vivo in the mouse model of PCa.
METHODS:
We detected the effects of roemerine on the proliferation, apoptosis and migration of PCa cells DU145, LNCaP, PC-3 and 22RV1, screened out the sensitive cell line and constructed a tumor-bearing model in mice for verification of the antitumor efficacy of roemerine in vivo.
RESULTS:
Roemerine inhibited the proliferation and migration of the DU145, LNCaP, PC-3 and 22RV1 cells and induced their apoptosis in different degrees, particularly those of the LNCaP cells. The average tumor weight was less in the roemerine intervention group ([1.99±0.95] g) than in the control ([2.95±1.04] g), the least in the high-dose roemerine (30 mg/kg) plus paclitaxel intervention group ([0.90±0.16] g). The mean heart, liver, and kidney indexes were markedly lower in the roemerine (0.58±0.06, 6.20±0.42 and 1.49±0.33) than in the paclitaxel group (0.66±0.04, 6.99±0.72 and 1.95±0.34), while the mean spleen and thymus indexes were remarkably higher in the former (0.54±0.11 and 0.06±0.01) than in the latter (0.41±0.09 and 0.05±0.01). Pathological staining showed a lower degree of malignancy and metastasis in both the roemerine and the roemerine + paclitaxel intervention group than in the control, as well as a lower degree of visceral injury in the roemerine and roemerine + paclitaxel groups than in the paclitaxel group.
CONCLUSIONS
Roemerine has some anti-PCa effect and alleviates adverse reactions in paclitaxel combination administration.
Alkaloids
;
therapeutic use
;
Animals
;
Antineoplastic Agents, Phytogenic
;
adverse effects
;
therapeutic use
;
Apoptosis
;
drug effects
;
Cell Line, Tumor
;
Cell Movement
;
drug effects
;
Cell Proliferation
;
drug effects
;
Disease Models, Animal
;
Drug Therapy, Combination
;
methods
;
Drugs, Chinese Herbal
;
therapeutic use
;
Male
;
Mice
;
Mice, Nude
;
Paclitaxel
;
adverse effects
;
therapeutic use
;
Prostatic Neoplasms
;
drug therapy
9.Efficacy and toxicity of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes.
Feng DU ; Peng YUAN ; Yang LUO ; Jiayu WANG ; Fei MA ; Ruigang CAI ; Ying FAN ; Qing LI ; Pin ZHANG ; Binghe XU ; Email: XUBINGHE@MEDMAIL.COM.CN.
Chinese Journal of Oncology 2015;37(10):788-792
OBJECTIVETo assess the efficacy of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes.
METHODSClinical data of 48 patients diagnosed and treated for mTNBC between 2004 and 2012 at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) were retrospectively analyzed. All patients were pretreated with anthracyclines and at least one taxane in neo-adjuvant, adjuvant or chemotherapy for mTNBC and patients should be having at least one measurable metastatic lesion. Totally, 48 patients were included in this study, of which 21 cases received first-line chemotherapy and 27 cases received second-line chemotherapy. Based on the regimen they received, 22 patients were treated with NVB plus platinum (NP), and 26 patients with NVB plus capecitabine (NX).
RESULTSAfter 70 months follow-up, in the total group of patients, the objective response rate was 20.8%, clinical benefit rate was 43.8%, median progression free survival (PFS) was 4.4 months and median overall survival (OS) was 15.5 months. In addition, the ORR was significantly better in the NP arm versus NX arm (33.8% vs.7.7%, P=0.029) as well as PFS was statistically improved in the NP arm than NX arm (5.3 m vs. 3.0 m, P=0.023). Similar trend was observed in the OS, although the difference was not statistically significant (27.7 m vs. 14.8 m, P=0.077). In all, the most frequently reported adverse events were G1/2 gastrointestinal toxicity (68.8%) and neutropenia (62.5%) . No significant difference was observed between the NP arm and NX arm (P>0.05). The percentage of patients who delayed chemotherapy administration in the NP arm and NX arm was 9.1% (n=2), and 3.8% (n=1), respectively.
CONCLUSIONSNVB-based combination chemotherapy demonstrates moderate efficacy in mTNBC patients pretreated with anthracyclines and one taxane with manageable toxicity. NP regimen shows potential superiority over NX regimen, and should be further verified in randomized phase III clinical trial in larger cohort.
Anthracyclines ; therapeutic use ; Antibiotics, Antineoplastic ; adverse effects ; therapeutic use ; Antineoplastic Agents, Phytogenic ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bridged-Ring Compounds ; therapeutic use ; Capecitabine ; administration & dosage ; Cisplatin ; administration & dosage ; Disease-Free Survival ; Humans ; Neutropenia ; chemically induced ; Retrospective Studies ; Taxoids ; therapeutic use ; Triple Negative Breast Neoplasms ; drug therapy ; pathology ; Vinblastine ; adverse effects ; analogs & derivatives ; therapeutic use
10.Cancer Therapy with Phytochemicals: Present and Future Perspectives.
Biomedical and Environmental Sciences 2015;28(11):808-819
Recently, a wide range of food-derived phytochemical compounds and their synthetic derivatives have been proposed for cancer treatment. Unfortunately, data available in related literature focus on the anti-cancer properties of compounds derived from edible plants, while very little is known about those derived from non-edible plants. And thus, the underlying mechanisms of their anti-cancer effects are yet to be elucidated. This review collates the available data on the anti-cancer activities of six phytochemical-derived compounds from edible and non-edible plants, i.e. rottlerin, berbamine, sparstolonin B, sulforaphane, plumbagin and 6-shogaol. These compounds are used as bioactive markers for cytotoxicity against tumors. As such, understanding their mode of action will provide the rationale for the combination strategies of these compounds with other drugs in the battle against cancer.
Acetophenones
;
pharmacology
;
therapeutic use
;
Antineoplastic Agents, Phytogenic
;
pharmacology
;
therapeutic use
;
Benzopyrans
;
pharmacology
;
therapeutic use
;
Benzylisoquinolines
;
pharmacology
;
therapeutic use
;
Catechols
;
pharmacology
;
therapeutic use
;
Heterocyclic Compounds, 4 or More Rings
;
pharmacology
;
therapeutic use
;
Humans
;
Isothiocyanates
;
pharmacology
;
therapeutic use
;
Naphthoquinones
;
pharmacology
;
therapeutic use
;
Neoplasms
;
drug therapy
;
Phytotherapy
;
Plant Extracts
;
pharmacology
;
therapeutic use
;
Signal Transduction
;
drug effects

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