ABSTRACT
Cervical cancer is among the leading causes of death in women. Chemotherapy options available for cervical cancer include highly cytotoxic drugs such as taxol, cisplatin, 5-florouracil, and doxorubicin, which are not specific. In the current study, we have identified a new peptide conjugate (Fur4-2-Nal3-Ala2-Phe1-CONH2) (conjugate 4), from screening of a small library of tripeptide-conjugates of furan, as highly potent anticancer compound against human cervical cancer cells (HeLa cells) (IC50 = 0.15 ± 0.05 µg/mL or 0.28 +/- 0.09 µM). Peptides were constructed on Rink amide resin from C- to N-terminus followed by capping by α-furoic acid moiety. The synthesized peptides were purified by recycling RP-HPLC, and structures of all the peptides were confirmed by using FABMS/ESIMS, 1H- NMR, 13C-NMR, and HR-FABMS. Conjugate 4 was furthermore found to be specifically active against human cervical cancer cells since it did not inhibit the proliferation of other human normal cells (HUVEC (human umbilical vein endothelial cells) and IMR-90 (normal human fibroblasts)), and cancer cells tested (HUVEC, MCF-7, and MDA-MB-231 cells), as well as in mice 3T3 cells (normal fibroblasts). This study revealed a good structure activity relationship of various peptide conjugates. Conjugate 4 in branched forms (4a and 4b) were also synthesized and evaluated against HeLa cells, and results revealed that both were inactive. Atomic force microscopy (AFM) studies and staining with rhodamine 123 and propidium iodide (PI) revealed that conjugate 4 possesses a membranolytic effect and causes the loss of mitochondrial membrane potential.
Subject(s)
Antineoplastic Agents/chemistry , Furans/chemistry , Peptides/chemistry , Uterine Cervical Neoplasms/drug therapy , 3T3 Cells , Amides , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation , Cell Survival/drug effects , Doxorubicin/pharmacology , Drug Screening Assays, Antitumor , Endothelial Cells/drug effects , Female , HeLa Cells , Human Umbilical Vein Endothelial Cells , Humans , Inhibitory Concentration 50 , MCF-7 Cells , Magnetic Resonance Spectroscopy , Mice , Microscopy, Atomic Force , Protein DomainsABSTRACT
OBJECTIVE: To identify the perceptions of rural women about modern contraceptive methods and to ascertain the psycho-social and economic attitude of women about family planning methods. METHODS: This cross-sectional study was conducted at the University of Sargodha, Sargodha, Pakistan, from December 2014 to March 2015, and comprised married women. The sample was selected using multistage sampling technique through Fitzgibbon table. They were interviewed regarding use of family planning methods. . SPSS 16 was used for data analysis. RESULTS: Of the 500 women, 358(71.6%) were never-users and 142(28.4%) were past-users of family planning methods. Moreover, 52(14.5%) of never-users did not know about a single modern contraceptive method. Of the past-users, 43(30.3%) knew about 1-3 methods and 99(69.7%) about 4 or more methods. Furthermore, 153(30.6%) respondents graded condoms as good, 261(55.2%) agreed that family planning helped in improving one's standard of living to a great extent while 453(90.6%) indicated that family planning methods were not expensive. Besides, 366(71.2%) respondents believed that using contraceptive method caused infertility. CONCLUSIONS: Dissatisfaction with methods, method failure, bad experiences with side effects, privacy concerns and different myths associated to the methods were strongly related to the non-usage of modern contraceptive methods.
