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Potential anticancer activity analysis of piscidin 5-like from Larimichthys crocea

Acta Oceanologica Sinica 2022年第3期41卷 53-60页

作者： Libing Zheng Jiayin Qiu Huihui Liu Changfeng Chi Longshan Lin National and Provincial Joint Laboratory of Exploration and Utilization of Marine Aquatic Genetic Resources School of Marine Science and TechnologyZhejiang Ocean UniversityZhoushan 316022China Third Institute of Oceanography Ministry of Natural ResourcesXiamen 361005China

Antitumor activity is one characteristic function of some certain antimicrobial peptides(AMPs)found in recent years.In the present study,we attempted to detect potential anticancer activity of a recombinant piscidin 5-like from Larimichthys crocea(r Lc-P5L)which owned widely antibacterial and strong antiparasitic activity in vitro.The light microscope observation indicated r Lc-P5L was of antitumor activity to He La cells,293 T cells and L929 cells.MTT assay showed the toxic sensitivity of r Lc-P5L to three tumor cell strains was 293 T>L929>He La.Scanning electron microscope(SEM)results showed r Lc-P5L behaved like a lytic peptide to cause damage on cells membrane of L929 cells by forming globular clusters,even pores at 60μmol/L,or degrading membrane to make it completely lose cytoskeleton structure at 80μmol/L;r Lc-P5L treatment also resulted in DNA degradation.Fluorescence observation results indicated r Lc-P5L could cause L929 cells at least two obvious changes:one is nucleus,nuclear chromatin condensed in the margin,nuclear volume became smaller and shrank to be out of shape,or lysed to be debris;the other is cytoskeleton,they became disordered and polarized to make cells atrophic shapes,or even lysed to be debris.In summary,r Lc-P5L owned potential anticancer activity causing membrane structure damage and genome DNA degradation.Interestingly,treatment with different concentration of r Lc-P5L seemingly caused the similar but different changes,whether it indeed gave rise to cancer cells diverse death way,the further studies should be performed,and the detailed mechanisms were still need further explored.

关键词： Larimichthys crocea piscidin 5-like anticancer activity membrane destruction DNA degradation

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anticancer activity of sodium caffeate and its mechanism

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Acta Pharmacologica Sinica 2005年第10期26卷 1248-1252页

作者： Feng XU~(2,3,4), Sheng-hua ZHANG~3, Rong-guang SHAO~3, Yong-su ZHEN~3 ~2 Department of Pharmacology Zhujiang Hospital, Southern Medical University Guangzhou 510280 ~3 Department of Ontology Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China Department of Pharmacology Zhujiang Hospital Southern Medical University Guangzhou China Department of Oncology Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

Aim: To study the anticancer activity of sodium caffeate （SC）. Methods: A nucleoside transport assay was used to analyze the inhibitory effects of SC on nucleoside rescue. The MTT assay was used to measure cell proliferation. Flow cytometrywas used to measure the apoptosis of BEC-7402 induced by SC and the cell cycledistribution change. Western blotting analysis was employed to investigate Bcl2, caspase and Bax expression. Intracellular Ca2+and mitochondrial membranepotential were determined by flow cytometry. In vivo anti-tumor activity wasmeasured using a tumor transplantation model in mice. Results: SC inhibited thenucleoside transport of BEL-7402 cells with an IC50of 1.02 mg/mL. SC inhibitedtumor cell proliferation with an IC50between 100 μg/mL and 200μg/mL. SC induced BEL-7402 cell apoptosis in a time-and dose-dependent manner, which wasinduced by arresting cells in S phase. The in vivo study showed that tumorgrowth was inhibited in a dose-dependent manner. Activated caspase-3 and Baxexpression were up-regulated after treatment with SC, while Bcl-2 expression wasdown-regulated. Intracellular Ca2+was increased while mitochondrial membranepotential was decreased by SC. Conclusion: SC is a new anticancer agent withpromising potential.

关键词： caffeic acid anticancer activity cell division cell apoptosis cell cycle phytogenic antineoplastic agent flow cytometry Western blotting

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Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells

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Chinese Journal of Integrative Medicine 2024年第1期30卷 25-33页

作者： GAO Quan LI Lin ZHANG Qi-man SHENG Qin-song ZHANG Ji-liang JIN Li-jun SHANG Rui-yan School of Pharmacy and Department of Medical Oncology the Affiliated Hospital of Hangzhou Normal UniversityHangzhou Normal UniversityHangzhou(311121)China Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhou(311121)China Department of Colorectal Surgery the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Beijing Tong Ren Tang Chinese Medicine Co. Ltd.Beijing(100000)China Department of Traditional Chinese Medicine Hangzhou Shangcheng District People's HospitalHangzhou(310006)China Department of Gynecology Hangzhou Women's HospitalHangzhou(310008)China

Objective: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer(CRC) through network pharmacology and molecular docking combined with experimental verification. Methods: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. Results: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase(Akt1, Akt2), cyclin-dependent kinase 6(CDK6), matrix metalloproteinase-9(MMP9), epidermal growth factor receptor(EGFR), cell division control protein 42 homolog(CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets(Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein(Panticancer role through Akt signaling pathway. Conclusions: Monotropein exerts its antitumor effects primarily by arresting the cell cycle,

关键词： monotropein Chinese medicine anticancer activity colorectal cancer cells network pharmacology

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anticancer activity of crude acetone and water extracts of Tulbaghia violacea on human oral cancer cells

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Asian Pacific Journal of Tropical Biomedicine 2018年第9期8卷 456-462页

作者： Samkeliso Takaidza Arumugam Madan Kumar Cornelius Cano Ssemakalu Nagabishek Sirpu Natesh Gayathri Karanam Michael Pillay Department of Biotechnology Vaal University of Technology Cancer Biology Lab Molecular and Nanomedicine Research Unit Sathyabama Institute of Science and Technology

Objective: To evaluate the anticancer activity of crude acetone and water leaf extracts of Tulbaghia violacea on a human oral cancer cell line(KB).Methods: The antioxidant activity of the leaf extracts was evaluated by using the DPPH assay while the anti-proliferative activity was assessed by using the MTT assay.The morphological characteristics of apoptotic cells were examined by using the dual acridine orange/ethidium bromide staining.Flow cytometry was used to evaluate the induction of multi-caspase activity and changes in the cell cycle.Results: The acetone and water extracts exhibited antioxidant activity in a concentration dependent manner.The extracts inhibited the growth of the KB cell line with IC_(50) values of 0.2 mg/mL and 1 mg/mL, respectively for acetone and water.Morphological changes such as cell shrinkage, rounding and formation of membrane blebs were observed in the treated cells.In acridine orange/ethidium bromide staining, the number of apoptotic cells increased as the concentration of the extracts increased.The activation of multi-caspase activity in KB cells treated with Tulbaghia violacea extracts was concentration dependent, leading to cell death by apoptosis and cell cycle arrest at the G_2/M phase.Conclusions: The acetone and water extracts of Tulbaghia violacea appear to have anti-cancer activity against human oral cancer cells and need to be investigated further.

关键词： anticancer activity Antioxidant Apoptosis Caspase Cell cycle Tulbaghia

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Thymoquinone enhances the antioxidant and anticancer activity of Lebanese propolis

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World Journal of Clinical Oncology 2023年第5期14卷 203-214页

作者： Sima AlDreini Zaynab Fatfat Najwa Abou Ibrahim Maamoun Fatfat Hala Gali-Muhtasib Hala Khalife Rammal Rammal Laboratory(ATAC Group) Faculty of Sciences IHadath 1003Lebanon Department of Biology American University of BeirutBeirut 1107-2020Lebanon Applied Biochemistry Laboratory School of PharmacyCamerino UniversityCamerino 62032Italy

BACKGROUND Reactive oxygen species(ROS)are produced by multiple cellular processes and are maintained at optimal levels in normal cells by endogenous antioxidants.In recent years,the search for potential exogenous antioxidants from dietary sources has gained considerable attention to eliminate excess ROS that is associated with oxidative stress related diseases including cancer.Propolis,a resinous honeybee product,has been shown to have protective effects against oxidative stress and anticancer effects against several types of neoplasms.AIM To investigate the antioxidant and anticancer potential of Lebanese propolis when applied alone or in combination with the promising anticancer compound Thymoquinone(TQ)the main constituent of Nigella sativa essential oil.METHODS Crude extracts of Lebanese propolis collected from two locations,Rashaya and Akkar-Danniyeh,were prepared in methanol and the total phenolic content was determined by Folin–Ciocalteu method.The antioxidant activity was assessed by the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl(DPPH)free radical and to inhibit H2O2-induced oxidative hemolysis of human erythrocytes.The anticancer activity was evaluated by[3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide]MTT assay against HCT-116 human colorectal cancer cells and MDAMB-231 human breast cancer cells.RESULTS The total phenolic content of propolis extract from Rashaya and Akkar-Danniyeh were 56.81μg and 83.503μg of gallic acid equivalent/mg of propolis,respectively.Both natural agents exhibited strong antioxidant activities as evidenced by their ability to scavenge DPPH free radical and to protect erythrocytes against H2O2-induced hemolysis.They also dose-dependently decreased the viability of both cancer cell lines.The IC50 value of each of propolis extract from Rashaya and Akkar-Danniyeh or TQ was 22.3,61.7,40.44μg/mL for breast cancer cells at 72 h and 33.3,50.9,33.5μg/mL for colorectal cancer cells at the same time point,respectively.Importantly,the inhibitory effects of propolis on

关键词： Lebanese propolis Thymoquinone Combination Antioxidant activity anticancer activity Phenolic compounds

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Praseodymium metal nanorods as a 5-fluorouracil carrier

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Journal of Rare Earths 2024年第7期42卷 1328-1336页

作者： Varnitha Manikantan Govindaraj Sri Varalakshmi Ujma Ashapak Tamboli Archana Sumohan Pillai Aleyamma Alexander Anushka Lucas Bose Allben Akash Israel V.M.V.Enoch Centre for Nanoscience and Genomics Karunya Institute of Technology and Sciences (Deemed University) Department of Applied Chemistry Karunya Institute of Technology and Sciences (Deemed University)

Interest in metal nanoparticles as nanoscale drug-carrying vehicles has been increasing.In such an aspect,lanthanide metal nanoparticles are particularly intriguing.Herein,we report praseodymium nanoparticles as a novel anticancer therapeutic transporting agent.The material was made as a composite with the supramolecular host polymer,poly-β-cyclodextrin.The praseodymium nanorods were characterized using standard analytical techniques,including X-ray diffraction（XRD）,X-ray photoelectron spectroscopy（XPS）,and thermogravimetric analysis（TGA）.In addition,they were imaged using transmission electron microscopy.The nanostructures are a long rod-shaped material with 2.0±0.1 μm in length and 230±10 nm in width.The material shows a saturation magnetization value above 30 emu/g with a coercivity value of 130 Oe.The nanocarrier is freighted with the drug 5-fluorouracil,and the encapsulation efficiency is 76.09%.The drug release is continuous from the nanocarrier（polymer-containing praseodymium nanoparticles） and proceeds for above 250 h.The in vitro cytotoxicities of the blank nanocarrier and the 5-fluorouracil-loaded one are deduced by testing them on MCF-7 and Vero（non-cancerous） cell lines.The cytotoxicity on the cancerous cell lines is observed,whereas the noncancerous cells are unaffected.The IC50values on the cell lines are reported.

关键词： anticancer activity Drug delivery Metal nanoparticles Poly-cyclodextrin Praseodymium Rare earths

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Lobelia chinensis: chemical constituents and anticancer activity perspective

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Chinese Journal of Natural Medicines 2014年第2期12卷 103-107页

作者： CHEN Mei-Wan CHEN Wen-Rong ZHANG Jin-Ming LONG Xiao-Ying WANG Yi-Tao State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macao School of Traditional Chinese Medicine Guangdong Pharmaceutical University

Research has demonstrated that many chemical constituents dominated by piperidine alkaloids and flavonoids, such as lobelanidine, lobeline, and lobelanine, have been obtained from Lobelia chinensis Lour. Experimental studies and clinical applications have also indicated that L. chinensis possesses a number of pharmacological activities(e.g., diuretic, choleretic, breathing excitement, anti-venom, anti-bacterial, and anticancer). This paper focuses on the properties, chemical constituents, and anticancer activity of L. chinensis to clarify the connection among them, and identify the active anticancer compounds. This work serves as the foundation for further research and development of L. chinensis.

关键词： Lobelia chinensis Chemical constituents anticancer activity

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Facile Synthesis of 7-epi-Taxane and Its Derivatives and Preliminary Evaluation of anticancer activity

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Chinese Journal of Chemistry 2016年第11期34卷 1165-1176页

作者： Zhao Li Jia Feng Kun Zou Zhuo Yang Yong Zhang Zhijian Xu Bo Li Jiye Shi Yiming Li Weiliang Zhu Kaixian Chen School of Pharmacy Shanghai University of Traditional Chinese Medicine Shanghai 201203 China CAS Key Laboratory of Receptor Research Drug Discovery and Design Centre Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 China Nano Science and Technology Institute University of Science and Technology of China Suzhou Jiangsu 215123 China UCB Biopharma SPRL Chemin du Foriest Braine-l'Alleud Belgium Kellogg College University of Oxford 60-62 Banbury Road Oxford OX2 6PN United Kingdom

7-epi-Taxane has been achieved efficiently in gram scale from natural taxane via inversion of the 7-hydroxyl group simply using Ag20 as catalyst and DMF as solvent. The catalyst could he quantitatively recovered by filtra- tion without loss of catalytic activity. This condition is also applicable to the direct epimerization of taxane derivatives （e.g., docetaxel and paclitaxel） to 7-epi-taxane derivatives （e.g., 7-epi-docetaxel and 7-epi-paclitaxel）. Furthermore, 33 ester derivatives of 7-epi-taxane with different amino acid moieties at the position of C-13 were successfully synthesized via esterification without protecting C-7-OH. Bioassay results revealed that compounds 13 and 18 have good selectivity against prostatic cancer cell line DU145, with ICs0 value as low as 15.9 nmol/L for 18.

关键词： taxane 7-epi-taxane silver oxide amino acid C-13 derivative of taxane anticancer activity

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Improvement of Stability and anticancer activity of ChlorambuciI-Tetrapeptide Conjugate Vesicles

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Chinese Journal of Chemistry 2016年第6期34卷 609-616页

作者： Wei Zhang Wenjun Zhu Ruiyu He Shuo Fang Yemin Zhang Chen Yao Muhammad Ismail Xinsong Li School of Chemistry and Chemical Engineering Southeast University Nanjing Jiangsu 210096 China

Chlorambucil is a classic nitrogen mustard drug that has been used in the treatment of cancers. It may induce neutropenia, thrombocytopenia and other side effects because of its short lifetime and off-target effect. In this report, chlorambucil-tetrapeptide （AAAK, A3K） conjugate vesicles were developed to improve the stability and bioactivity of chlorambucil. First of all, chlorambucil-A3K conjugate was synthesized by solid phase synthesis strategy. Sec- ondly, the chlorambucil-A3K conjugate was assembled and characterized by critical aggregation concentration, cir- cular dichroism, dynamic light scattering and transmission electron microscopy. The results indicated that the chlo- rambucil-A3K conjugate can be assembled to form spherical vesicles with an average diameter of 390.5 nm, and high drug loading about 47.1% is reached. Surprisingly, the preliminary biological evaluation of the chlorambu- cil-A3K conjugate vesicles revealed the best in vitro anticancer activity against HeLa, HepG-2 and MCF-7 cell lines compared with chlorambucil and chlorambucil-A3K conjugate free drugs. Furthermore, conjugate vesicles showed excellent in vivo antitumoral activity. It can be partly attributed to their vesicular structure which isolates chloram- bucil active moiety from aqueous solution to retard degradation before killing cancer cells. Therefore, chlorambu- cil-peptide （A3K） conjugate vesicles may be an alternative delivery system of chlorambucil.

关键词： chlorambucil-tetrapeptide conjugate self-assembly vesicles anticancer activity

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Total synthesis and anticancer activity studies of the stereoisomers of asperphenamate and patriscabratine

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Chinese Chemical Letters 2010年第2期21卷 155-158页

作者： Yuan, Lei Wang, Jin Hui Sun, Tie Min Shenyang Pharmaceut Univ Sch Pharmaceut Engn Shenyang 110016 Peoples R China Shenyang Pharmaceut Univ Sch Traditt Chinese Mat Med Shenyang 110016 Peoples R China

All stereoisomers of asperphenamate 1a and patriscabratine 2a were achieved with a high yield, and total synthesis of 2a is firstly described here. The absolute configuration of patriscabratine was determined as ( S , S ). The compounds 1a – d and 2a – d have been tested by MTT assay in T47D, MDA-MB231, HL60, Hela and SGC-7901 cell lines in vitro . Among them, the ( R , S ) stereoisomer shows the strongest anticancer effects, while the ( S , R ) shows the weakest one.

关键词： N N -substituted phenylalanine-phenylalaninol ester Asperphenamate Patriscabratine Total synthesis anticancer activity

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