Natural Plant-derived Polysaccharides Against Cervical Cancer： A Review / 中国实验方剂学杂志

Cervical cancer is a gynecological malignant tumor with a high incidence in the world. With the insidious onset and lack of obvious symptoms and signs in the early stage， 13% of cervical cancer patients are diagnosed in the advanced stage of the disease， and the 5-year survival rate of metastatic cervical cancer is only 16.5%. So far， surgery and radiotherapy/chemotherapy are still the basic means for the treatment of cervical cancer. However， with the emergence of toxicity， drug resistance， and other side effects， there are still some limitations in the clinical application of these therapies. In recent years， natural compounds represented by polysaccharides have been found to have a significant anti-cervical cancer effect， which has attracted extensive attention from researchers in China and abroad. Widely distributed in the roots， stems， leaves， flowers， and fruits of higher plants， plant-based polysaccharides are important components of natural polysaccharides， as well as multimers with a complex structure and biological response regulators， which have been widely studied in the fields of cancer， cardiovascular， endocrine， and other diseases. This study reviewed the research on the anti-cervical cancer effect and mechanism of natural plant-derived polysaccharides by consulting the literature in the past 20 years to bring breakthroughs in the research and development of anti-cervical cancer new drugs. Through the literature review， the results indicated that natural plant-derived polysaccharides could exert anti-tumor effects by inhibiting cell proliferation， promoting apoptosis， inhibiting invasion and migration， promoting autophagy， arresting cell cycle of cervical cancer cells， regulating epithelial-mesenchymal transition （EMT）， resisting oxidative stress， inhibiting tumor angiogenesis， improving immunomodulatory activity， and regulating signaling pathways. It should be noted that in the current research on natural plant-derived polysaccharides against cervical cancer， the bioavailability of some natural polysaccharides is low and a considerable proportion of the research is limited to the in vitro experiment. Therefore， it is urgent to carry out more clinical experimental studies on the anti-cervical cancer of natural plant-based polysaccharides to obtain a more reliable theoretical and practical basis.

MS-5, a Naphthalene Derivative, Induces the Apoptosis of an Ovarian Cancer Cell CAOV-3 by Interfering with the Reactive Oxygen Species Generation

Reactive oxygen species (ROS) are widely generated in biological processes such as normal metabolism and response to xenobiotic exposure. While ROS can be beneficial or harmful to cells and tissues, generation of ROS by diverse anti-cancer drugs or phytochemicals plays an important role in the induction of apoptosis. We recently identified a derivative of naphthalene, MS-5, that induces apoptosis of an ovarian cell, CAOV-3. Interestingly, MS-5 induced apoptosis by down-regulating the ROS. Cell viability was evaluated by water-soluble tetrazolium salt (WST-1) assay. Apoptosis was evaluated by flow cytometry analysis. Intracellular ROS (H₂O₂), mitochondrial superoxide, mitochondrial membrane potential (MMP) and effect on cycle were determined by flow cytometry. Protein expression was assessed by western blotting. The level of ATP was measured using ATP Colorimetric/Fluorometric Assay kit. MS-5 inhibited growth of ovarian cancer cell lines, CAOV-3, in a concentration- and time-dependent manner. MS-5 also induced G1 cell cycle arrest in CAOV-3 cells, while MS-5 decreased intracellular ROS generation. In addition, cells treated with MS-5 showed the decrease in MMP and ATP production. In this study, we found that treatment with MS-5 in CAOV-3 cells induced apoptosis but decreased ROS level. We suspect that MS-5 might interfere with the minimum requirements of ROS for survival. These perturbations appear to be concentration-dependent, suggesting that MS-5 may induce apoptosis by interfering with ROS generation. We propose that MS-5 may be a potent therapeutic agent for inducing apoptosis in ovarian cancer cell through regulation of ROS.

Curcumin,from health product to medicine / 中国药理学与毒理学杂志

Curcumin is the principal curcuminoid of the rhizomes of Curcuma longa(turmeric,Jiang Huang), which has more than 6000 years of application history in India and other Asian countries. At present,curcumin is sold as an herbal supplement,cosmetics ingredient,food flavoring,and food coloring. In China curcumin is mainly used in food, while in western countries it has been regarded as a health care product and is contained in the British Pharmacopoeia (2017), United States Pharmacopeia (40) and European Pharmacopoeia (8.7th ed.). Curcumin has been proved to have multiple pharmacology effects including anti-fibrosis, anti-tumor, anti-inflammation effects and so on. As its broad biological activities, it is applicated in a lot of diseases such as hyperlipidemia, infection and cancer. Among them, the anti-cancer effect of curcumin is the most attractive. In the treatment of cancer and related diseases, curcumin has been tested in phase I and II clinical trials in several research centers across the world and has been approved by the U.S.FDA into the phase III clinical trial.It has been listed as the third generation of cancer chemoprevention agent by the U.S.National Cancer Institute.Curcumin has been proved to inhibit the proliferation of a variety of tumor cells through regulating a variety of tran-scription factors(NF-κB,AP-1,etc),mitogen-activated protein kinase(MAPK),growth factor receptor ki-nase(PDGFR,VEGFR,etc)and cyclooxygenase.It plays an important role in the cell cycle and further to inhibit proliferation.Curcumin can also inhibit the migration of tumor cells by activating caspase and in-ducing tumor cell apoptosis.However,curcumin still needs researches to confirm its effects and mecha-nisms and find its exact indications. There is still a long way to go to make curcumin better applied in clinical practice in the further.

Effects of Guttiferone K on Inducing G0/1 Arrest of Prostate Cancer LNCaP Cells / 世界科学技术-中医药现代化

This study aimed at investigating the effects of Guttiferone K (GUTK),a polycyclic polyprenylated acylphloroglucinols (PPAPs) compound isolated from Garcinia yunnanensis,on the cell proliferation of human prostate cancer LNCaP cell line.Human prostate cancer LNCaP cells in the period of logarithmic phase were treated with GUTK.MTI assay was used to detect cell proliferation.Flow cytometry of propidium iodide (PI) staining,BrdU assay and immunocytochemistry were adopted to analyze the cell cycle phase distribution.Protein levels of Cyclin A,p27 and SKP2 were detected by western blotting.The results showed that GUTK inhibited the proliferation and induced G0/1 arrest of LNCaP cells in a time and dose dependent manner.The protein levels of Cyclin A and SKP2 were decreased,while p27 was increased by GUTK in human prostate cancer LNCaP cells.It was concluded that GUTK,a compound isolated from G.yunnanensis,presented the effect of inhibiting the cell proliferation by inducing G0/1 arrest of human prostate cancer LNCaP cells,with potential anti-prostate cancer action.

Anti-cancer Mechanism of Docosahexaenoic Acid in Pancreatic Carcinogenesis: A Mini-review

Pancreatic cancer is a highly aggressive malignant tumor of the digestive system and radical resection, which is available to very few patients, might be the only possibility for cure. Since therapeutic choices are limited at the advanced stage, prevention is more important for reducing incidence in high-risk individuals with family history of pancreatic cancer. Epidemiological studies have shown that a high consumption of fish oil or ω3-polyunsaturated fatty acids reduces the risk of pancreatic cancers. Dietary fish oil supplementation has shown to suppress pancreatic cancer development in animal models. Previous experimental studies revealed that several hallmarks of cancer involved in the pathogenesis of pancreatic cancer, such as the resistance to apoptosis, hyper-proliferation with abnormal Wnt/β-catenin signaling, expression of pro-angiogenic growth factors, and invasion. Docosahexaenoic acid (DHA) is a ω3-polyunsaturated fatty acid and rich in cold oceanic fish oil. DHA shows anti-cancer activity by inducing oxidative stress and apoptosis, inhibiting Wnt/β-catenin signaling, and decreasing extracellular matrix degradation and expression of pro-angiogenic factors in pancreatic cancer cells. This review will summarize anti-cancer mechanism of DHA in pancreatic carcinogenesis based on the recent studies.

Establishment of an Allo-Transplantable Hamster Cholangiocarcinoma Cell Line and Its Application for In Vivo Screening of Anti-Cancer Drugs

Opisthorchis viverrini (O. viverrini) is a well-known causative agent of cholangiocarcinoma (CCA) in humans. CCA is very resistant to chemotherapy and is frequently fatal. To understand the pathogenesis of CCA in humans, a rodent model was developed. However, the development of CCA in rodents is time-consuming and the xenograft-transplantation model of human CCA in immunodeficient mice is costly. Therefore, the establishment of an in vivo screening model for O. viverrini-associated CCA treatment was of interest. We developed a hamster CCA cell line, Ham-1, derived from the CCA tissue of O. viverrini-infected and N-nitrosodimethylamine-treated Syrian golden hamsters. Ham-1 has been maintained in Dulbecco's Modified Essential Medium supplemented with 10% fetal bovine serum for more than 30 subcultures. These cells are mostly diploid (2n=44) with some being polyploid. Tumorigenic properties of Ham-1 were demonstrated by allograft transplantation in hamsters. The transplanted tissues were highly proliferative and exhibited a glandular-like structure retaining a bile duct marker, cytokeratin 19. The usefulness of this for in vivo model was demonstrated by berberine treatment, a traditional medicine that is active against various cancers. Growth inhibitory effects of berberine, mainly by an induction of G1 cell cycle arrest, were observed in vitro and in vivo. In summary, we developed the allo-transplantable hamster CCA cell line, which can be used for chemotherapeutic drug testing in vitro and in vivo.

Research progress in the effect and mechanism of electric field in treating tumors / 国际生物医学工程杂志

Treating tumors with electric field is an interdisciplinary integrated and comprehensive research which applies electro-technology to tumor treatment.This therapy has the characteristics of safe,practical to its users and the parameters are easily to be controlled,which has attracted considerable attention in recent years.The main types of electric field in current research or application are pulsed electric field and direct current electric field.Both of the types can change the environment where tumors grow with different mechanisms,and the tumors would be killed through their pathological changes.Alternating electric field in intermediate frequency is a new type of tumor treating field,which has a promising application prospect.This article reviews the international and domestic research progress of the effects and mechanisms of the three kinds of electric fields used in the treatment of tumors.

Anti-tumor and immunoenhancement effects of effective combination of extraction from edible fungi on C26 xenograft mice / 中国癌症杂志

Background and purpose:Edible fungi has shown powerful potential in health care. This study aimed to explore the anti-tumor and immunoenhancement effects of combination of extraction from edible fungi. Methods:C26 cells has been xenografted into mice, and the animal models were randomly divided into control group, prevention group, treatment group and cyclophosphamide group. Mice were given the combination of extraction from edible fungi every day after vaccination of C26 cells into mice, except the prevention group which has been given the combination of extraction from edible fungi two weeks before vaccination. Two weeks after being planted, all the mice were killed and the tumor inhibition rates were studied. The immune function was measured by T lymphocyte transforming assay and NK killing assay. Results:There were signif icant difference in terms of tumor weight between prevention group and control group. The prevention group mice display improved T lymphocyte transforming assay and NK killing ability. Conclusions:The combination of extraction from edible fungi has remarkable inhibitory effects on C26 carcinoma in mice and can enhance immunity against mice with C26 carcinoma.

Anticancer effect of tamoxifen in oral cancer cell

Tamoxifen is an selective estrogen receptor antagonist widely used in the management of patients with breast cancer for more than 30 years. It was thought to act primarily through occupying the estrogen receptor sites in ER positive breast cancer cells and directly on cancer cell proper. These inhibitory effects, which have been shown to be independent of the ER, highlight new mechanism of therapeutic action of tamoxifen. The purposes of this study were to identify ER in oral carcinoma cell lines and to evaluate ER independent cytotoxic effect of tamoxifen. KB(SCC), HSC-3(SCC) and A253(ACC) cell line were used and capacity of cell proliferation, apoptosis, in vitro invasion and gelatin zymography were tested. ER expression of each cell line were detected by RT-PCR and immunocytochemistry. Dose dependent inhibition of cell proliferation and inhibition of gelatinolytic activity were observed in all oral carcinoma cell lines and significant difference of apoptotic index were observed in A253 and KB. Tamoxifen inhibited in vitro invasion in all experimental groups. ER expression was detected in KB and A253. These data suggest that tamoxifen may play a role in management of oral carcinoma by independent cytotoxic effect and more advanced research must processed confirming ER-dependent cytotoxicity.

The anti-tumour effect of Wuxing soup and its effect on the immunity of melanoma mice / 中国癌症杂志

Background and purpose:Wuxing soup is popular for it's anti-cancer effect in folk medicine and deserved to be further studied by modern scientific methods.This research aimed to explore its anti-cancer effect and to study the influence on the immunity of melanoma in mice. Methods :Inhibition of different ingredients and concentrations of Wuxing soup on the growth of the mouse melanoma B16 cells was detected by MTT in vitro.Animal experiment was performed to determine its anti-cancer effect in vivo.C57/BL6 mice were randomly divided into three groups after vaccination of B16 cell,and then given intragastrically with different soups for 25 days.All mice were killed on day 26 after inoculation.The weight of tumors were recorded.The anti-tumor immune function was measured by T lymphocyte transforming assay and NK killing assay.The different effect of different ingredients was also observed. Results :Our result showed that different ingredients soup exerted different inhibition on B16 cell growth and Wuxing soup was the strongest one of all and in dose-dependent manner in vitro.The animal experiment indicated that different ingredients soup has different inhibition on melanoma,the soup-treated mouse display improved T lymphocyte transforming assay and NK killing ability.Among the different soups,Wuxing soup showed the strongest anti-cancer effect and immune enhancement. Conclusions :Wuxing soup is an effective anti-cancer agent in melanoma mice and can enhance the immunity of the mice with melanoma.