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A mini-review and perspective on ferroptosis-inducing strategies in cancer therapy

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Chinese Chemical Letters 2019年第4期30卷 847-852页

作者： Shuaifei Wang Hongwei Liao Fangyuan Li Daishun Ling Institute of Pharmaceutics College of Pharmaceutical Sciences Zhejiang University Hangzhou Institute of Innovative Medicine College of Pharmaceutical Sciences Zhejiang University Key Laboratory of biomedical Engineering of the Ministry of Education College of Biomedical Engineering & Instrument Science Zhejiang University

Ferroptosis, as a new type of cell death caused by lipid peroxidation, has attracted much attention since it was first identified in 2012. A lot of progress has been made in unraveling its mechanisms and therapeutic potential as a target for cancer therapy. Hitherto, there are mainly two strategies widely adopted for designing ferroptosis-inducing agents, which include increasing the intracellular reactive oxygen species(ROS) level by Fenton reaction, and inactivating the glutathione peroxidase 4(GPX4). In this mini-review,we summarize the recent advances in ferroptosis-based anticancer treatments with a highlight on nanomaterials, and discuss the current challenges faced by those agents from the perspective of in vivo applications. Moreover, by generalizing ferroptosis induced by excess iron ions to cell death caused by the polyvalent metal-mediated oxidative burden, we introduce a new paradigm of cancer treatment by exploiting various polyvalent metals to disrupt the vulnerable redox balance in cancer cells, which may greatly diversify our arsenal to combat cancer.

关键词： Ferroptosis Fenton reaction Reactive oxygen species Lipid peroxidation Glutathione peroxidase 4

The role of vitamin D in cancer prevention

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Chinese Journal of Natural Medicines 2015年第7期13卷 481-497页

作者： Rachel A.Ness Duane D.Miller Wei LI department of pharmaceutical sciences University of Tennessee Health Sciences Center

Vitamin D,also known as cholecalciferol,is the precursor to the active steroid hormone 1,25-dihydroxyvitamin D3(calcitriol; 1,25(OH)2D3).The main physiological role for 1,25(OH)2D3 is to regulate calcium and inorganic phosphate homeostasis for bone *** recently,vitamin D has been investigated for its effects in the prevention and treatment of a variety of diseases such as cancer,autoimmune disorders,and cardiovascular *** data strongly support a role for vitamin D in the prevention of cancer through its anti-proliferative,pro-apoptotic,and anti-angiogenic effects on *** and clinical studies have shown mixed data on the correlation between serum vitamin D levels and cancer *** report seeks to outline results from the most recent preclinical and clinical studies investigating the potential role of vitamin D in cancer prevention.

关键词： Vitamin D Calcitriol Cancer prevention Cancer prognosis Vitamin D deficiency

Isoniazid metabolism and hepatotoxicity

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Acta Pharmaceutica Sinica B 2016年第5期6卷 384-392页

作者： Pengcheng Wang Komal Pradhan Xiao-bo Zhong Xiaochao Ma Center for Pharmacogenetics Department of Pharmaceutical SciencesSchool of PharmacyUniversity of Pittsburgh department of pharmaceutical sciences School of PharmacyUniversity of Connecticut

Isoniazid(INH) is highly effective for the management of ***,it can cause liver injury and even liver *** metabolism has been thought to be associated with INH-induced liver *** review summarized the metabolic pathway... 详细信息

关键词： Isoniazid Metabolism Hepatotoxicity Anti-tuberculosis N-Acetyltransferase 2 Amidase

The potential of standardized quassinoid-rich extract of Eurycoma longifolia in the regulation of the oestrous cycle of rats

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Asian Pacific Journal of Tropical Biomedicine 2017年第1期7卷 27-31页

作者： Suzanah Abdul Rahman Nur Amalina Ahmad Nadia Hanis Abdul Samat Syazana Zahri Afif Raihan Abdullah Kit-Lam Chan department of biomedical Science Kulliyyah of Allied Health SciencesInternational Islamic University Malaysia School of pharmaceutical sciences Universiti Sains Malaysia

Objective: To evaluate the effects of Eurycoma longifolia(E. longifolia) standardized extract on the oestrous cycle, levels of reproductive hormones and histology of the ovaries of Sprague-Dawley ***: Female rats were orally treated with E. longifolia standardized extract at the dose levels of 2.5, 5.0, 10.0, 25.0, 50.0 and 100.0 mg/kg of body weight over 5 *** smears were monitored daily within the duration and after withdrawal of the treatment before being sacrificed. The body weights of the females were recorded before and after the 5 days treatment. At the end of the experiments, blood samples were collected for determination of testosterone, oestradiol and progesterone levels. Ovaries were removed, weighed and examined for histomorphological ***: The administration of E. longifolia standardized extract did not significantly alter the oestrous cycle of the rats during the 5 days treatment and after withdrawal of the treatments. This was supported by normal testosterone, oestradiol and progesterone levels as well as normal morphology of the ***: The data obtained showed that E. longifolia standardized extract did not exhibit any toxic effect on reproductive activities of female rats suggesting potential use in the management of infertility.

关键词： Eurycoma longifolia Oestrous cycle Testosterone Oestradiol Progesterone Ovaries

Insoluble drug delivery strategies: review of recent advances and business prospects

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Acta Pharmaceutica Sinica B 2015年第5期5卷 442-453页

作者： Sandeep Kalepu Vijaykumar Nekkanti department of pharmaceutical Technology Shri Vishnu College of Pharmacy College of pharmaceutical sciences Western University of Health Sciences

The emerging trends in the combinatorial chemistry and drug design have led to the development of drug candidates with greater lipophilicity, high molecular weight and poor water solubility. Majority of the failures in new drug development have been attributed to poor water solubility of the drug. Issues associated with poor solubility can lead to low bioavailability resulting in suboptimal drug delivery. About 40% of drugs with market approval and nearly 90% of molecules in the discovery pipeline are poorly water-soluble. With the advent of various insoluble drug delivery technologies, the challenge to formulate poorly water soluble drugs could be achieved. Numerous drugs associated with poor solubility and low bioavailabilities have been formulated into successful drug products. Several marketed drugs were reformulated to improve ef fi cacy, safety and patient compliance. In order to gain marketing exclusivity and patent protection for such products, revitalization of poorly soluble drugs using insoluble drug delivery technologies have been successfully adopted by many pharmaceutical *** review covers the recent advances in the fi eld of insoluble drug delivery and business prospects.

关键词： Bioavailability Cocrystals Solubility Inclusion complexation Nanoparticles Self-emulsifying formulations Proliposomes

The genetic variation in Monocarboxylic acid transporter 2 （MCT2） has functional and clinical relevance with male infertility

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Asian Journal of Andrology 2014年第5期16卷 694-697,I0007页

作者： Jinu Lee Dong Ryul Lee Suman Lee Yonsei Institute of pharmaceutical sciences College of Pharmacy Yonsei University Incheon department of biomedical Science CHA University Seongnam-si Korea

Monocarboxylic acid transporter 2 （MCT2） transports pyruvate and lactate outside and inside of sperms, mainly as energy sources and plays roles in the regulation of spermatogenesis. We investigated the association among genetic variations in the MCT2 gene, male infertility and MCT2 expression levels in sperm. The functional and genetic significance of the intron 2 （＋28201A 〉 G, rs10506398） and 3＇ untranslated region （UTR） single nucleotide polymorphism （SNP）（＋2626G 〉 A, rs10506399） of MCT2 variants were investigated. Two MCT2 polymorphisms were associated with male infertility （n = 471, P 〈 0.05）. In particular, the MCT2-3＇ UTR SNP （＋2626 G 〉 A） had a strong association with the oligoasthenoteratozoospermia （OAT） group. The ＋2626GG type had an almost 2.4-fold higher sperm count than that of the ＋2626AA type （＋2626GG; 66 x 106 vs ＋2626AA; 27 x 106, P 〈 0.0001）. The MCT2-3＇ UTR SNP may be important for expression, as it is located at the MCT2 3＇ UTR. The average MCT2 protein amount in sperm of the ＋2626GG type was about two times higher than that of the ＋2626AA type. The results suggest that genetic variation in MCT2 has functional and clinical relevance with male infertility.

关键词： 3' UTR male infertility monocarboxylic acid transporter 2 single nucleotide polymorphism sperm

Inhibition of platelet aggregation by polyaspartoyl L-arginine and its mechanism

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Acta Pharmacologica Sinica 2004年第4期25卷 71-75页

作者： Yin-ye WANG, Zhi-yu TANG, Min DONG, Xiao-yan LIU, Shi-qi PENG2 department of Pharmacology, department of Medicinal Chemistry, 2 Schoolof pharmaceutical sciences, Peking University, Beijing 100083, China department of Pharmacology School of pharmaceutical sciences Peking University 北京 100083 department of Medicinal Chemistry School of Pharmaceutical Sciences Peking University 北京 100083

AIM: To observe the oral anti-platelet efficacy and the potential action mechanism of polyaspartoyl L-arginine (PDR), a new L-arginine rich compound. METHODS: Platelet aggregation was conducted by Born’s method; bleeding time was determined using tail’s bleeding time in mice; platelet adhesion was carried out with glass bottle method; nitric oxide (NO) was tested with Griess’ method; and cAMP, thromboxane B2 (TXB2) and 6-keto-PGF1α were assessed with commercial kits. RESULTS: The inhibition by PDR (15-60 mg/kg ig or 10 mg/kg iv) of platelet aggregation induced by adenosine diphosphate (ADP), collagen or thrombin at 1 h after oral administration or at 20 min after iv injection for rats (P<0.01), and its (15 mg/kg, ig) inhibition of ADP-induced platelet aggregation for rabbits during 6 h after administration were observed. PDR (15-60 mg/kg) prolonged the bleeding time of mice (P<0.05) and (30 mg/kg) increased NO concentration in plasma. On the other hand PDR did not change the contents of cAMP in platelet and TXB2 or 6-keto-PGF1α in plasma. CONCLUSION: PDR is a novel, oral effective platelet aggregation inhibitor and its action mechanism possibly related to increasing NO generation.

关键词： platelet aggregation bleeding time platelet adhesiveness polyaspartoyl L-arginine nitric oxide cyclic AMP Thromboxane B2 6-ketoprostaglandin F1 alpha

A Cationic [60] Fullerene Derivative Reduces Invasion and Migration of HT-29 CRC Cells in Vitro at Dose Free of Significant Effects on Cell Survival

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Nano-Micro Letters 2014年第2期6卷 163-168页

作者： Marianna Lucafò Chiara Pelillo Marco Carini Tatiana Da Ros Maurizio Prato Gianni Sava department of Life sciences University of Trieste department of Chemical and pharmaceutical sciences University of Trieste

Nanomaterials with unique characteristics exhibit favorable therapeutic and diagnostic properties,implying their enormous potential as biomedical candidates. C60 has been used in gene- and drug-delivery, as imaging agents, and as photosensitizers in cancer therapy. In this study, the influences of a cationic functionalized fullerene on cellular behavior of human colorectal cancer cell line(HT-29) were investigated. Results indicated that HT-29 treated with the studied compound showed a lower sensitivity but a significant impairment in migration and invasion by interfering with the activities of matrix metalloproteinases(MMP-2 and9). The presence of fullerene also altered the capacity of adhesion-related proteins to perform their activity,thereby inducing dramatically adverse effects on the cell physiological functions such as cell adhesion. Thus,our study suggests that this compound is a new potential anti-metastatic effector and a therapeutic component for malignant colorectal cancer.

关键词： Fullerene Cancer Anti-metastatic drug Nanomedicine

Antioxidant activity and phenol and flavonoid contents of eight medicinal plants from Western Nepal

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Journal of Traditional Chinese Medicine 2014年第5期34卷 584-590页

作者： Lalita Subedi Sunita Timalsena Pabitra Duwadi Ritu Thapa Anita Paudel Kalpana Parajuli department of pharmaceutical sciences School of Health and Allied SciencesPokhara University

OBJECTIVE: The purpose of this study was to evaluate the antioxidant activity, phenolic and flavonoids contents of selected medicinal plants form the Western region of ***: The antioxidant activity of selected medicinal plants were determined by using 2, 2-diphenyl-1-picrylhydrazyl radical scavenging activity; total ferric ion reducing ability through spectroscopic analysis. The content of total phenols was determined using Folin-Ciocalteu reagent, whereas Aluminum chloride colorimetric method was used for flavonoid ***: Extracts of Syzygium Operculatus(87%),Astilbe Rivularis(83%) and Mallotus Philippnensis(88%) showed significant free radical scavenging activity with effective concentration(EC50) close to that of ascorbic acid. Syzygium Operculatus(96%),Astilbe Rivularis(97%) and Mallotus Philippnensis(97%) had potent reducing power in concentration dependent fashion. Those plant extract with higher free radical scavenging and ferric reducing effect also showed the greater content of both phenols and flavonoids, suggesting the correlation between polyphenolic content and antioxidant activity. Those plant extracts which showed better antioxidant activity assays, also demonstrated higher total phenol and flavonoid contents. These three plants showed the presence of higher amount of phenols and ***: This study may provide the scientific basis for the traditional use of those plants and may provide valuable idea for further research.

关键词： Plants, medicinal Antioxidants 2, 2-di-phenyl-l-picrylhydrazyl Phenol Flavonoids