tamoxifen-citrate and Breast-Neoplasms

Topics: Animals; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Carbazoles; Caspases; Cell Line, Tumor; Down-Regulation; Humans; Inhibitory Concentration 50; PC-3 Cells; Polymerization; Proto-Oncogene Proteins c-akt; Pyrans; Rats; TOR Serine-Threonine Kinases; Tubulin

When using selective estrogen receptor modulators (SERMs) in cancer therapy, adverse effects such as endothelial dysfunction have to be considered. Estrogens and, consequently, SERMs regulate the synthesis of vasoactive nitric oxide (

Topics: Alkenes; Antineoplastic Agents; Breast Neoplasms; Cell Proliferation; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Human Umbilical Vein Endothelial Cells; Humans; Melanoma; Nitric Oxide Donors; Selective Estrogen Receptor Modulators; Therapeutic Index

A diverse library of chromene-xanthene hybrids were synthesized through intramolecular Friedel-Crafts reaction of the arenoxy carbinols. Examples include first incorporation of amino acid tyrosine into xanthene skeletons with polar functionalities. A careful structural evaluation revealed that tyrosine crafted chromene-xanthene hybrids exhibited good activities against breast cancer cell lines MCF-7, MDA-MB-231. The lead compound 16 displays significant cell cycle arrest at G1 phase and induces apoptosis in MDA-MB-231 cells.

Topics: Antineoplastic Agents; Apoptosis; Benzopyrans; Breast Neoplasms; Cell Line, Tumor; G1 Phase Cell Cycle Checkpoints; HEK293 Cells; Humans; Molecular Structure; Tamoxifen; Xanthenes

A series of new benzoxazepine derivatives substituted with different alkoxy and aryloxy group were synthesized comprising synthetic steps of Mitsunobu reaction, lithium aluminum hydride (LAH) reduction, followed by debenzylation and finally intramolecular Mitsunobu cyclization. The new benzoxazepines specifically inhibited growth of breast cancer cell lines, MCF-7 and MDA-MB-231, but lack cytotoxicity to normal HEK-293 cells. The cell growth inhibition induced by the active compounds was due to cell cycle arrest at G(0)/G(1) phase. The active compound could cause significant reduction in tumor volume of MCF-7 xenograft tumor in nude mice model and their activity was comparable to that of tamoxifen citrate at 16mgkg(-1) dose at 30days of treatment. The identified most active compounds of the series have specific advantages as anti-cancer agent in breast cancer than tamoxifen.

Topics: Aluminum Compounds; Animals; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cyclization; Female; G1 Phase; Humans; Lithium Compounds; Mice; Mice, Nude; Oxazepines; Resting Phase, Cell Cycle; Structure-Activity Relationship; Tamoxifen; Xenograft Model Antitumor Assays

Neo-tanshinlactone (1) was isolated and synthesized for the first time and evaluated in vitro against several human cancer cell lines. Compound 1 showed significant inhibition against two ER+ human breast cancer cell lines and was 10-fold more potent and 20-fold more selective as compared to tamoxifen citrate. Compound 1 also potently inhibited an ER-, HER-2 overexpressing breast cancer cell line. Therefore, this novel compound merits further development as an anti-breast cancer drug candidate.

Topics: Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Line, Tumor; Drug Screening Assays, Antitumor; Female; Furans; Humans; Pyrones; Receptor, ErbB-2; Receptors, Estrogen; Salvia miltiorrhiza

1,1,2-Triphenylbut-1-enes (E- and Z-10-12), which are substituted with one p- and one m-acetoxy group in two different aromatic rings, were synthesized. The E and Z isomers were isolated, and their identity was established by 1H NMR spectroscopy. A study of the structure-activity relationship was carried out with regard to estradiol receptor affinity in vitro, estrogenic and antiestrogenic properties (mouse), inhibition of the hormone-dependent human MCF7 breast cancer cell line in vitro, and the hormone-dependent MXT mammary tumor of the mouse in vivo. Among the tested compounds, (E)- and (Z)-1-(3-acetoxyphenyl)-1-(4-acetoxyphenyl)-2-phenylbut-1-enes+ ++ (E-10 and Z-10) and (Z)-1-(3-acetoxyphenyl)-1-phenyl-2-(4-acetoxyphenyl)-but-1-ene (Z-12) proved to be partial antiestrogens, which lead to an inhibition of the MCF7 cell line. They exert a growth-inhibiting activity on the hormone-dependent MXT mammary carcinoma of the mouse. In the case of E-10 and Z-10, this effect is only slightly weaker than that of 1,1-bis(4-acetoxyphenyl)-2-phenylbut-1-ene (13) and tamoxifen. Under the applied experimental conditions, there were no significant changes of uterine weight as an indicator of estrogenic side effects.

Topics: Alkenes; Animals; Breast Neoplasms; Cell Line; Chemical Phenomena; Chemistry; Estrogen Antagonists; Female; Humans; Isomerism; Mammary Neoplasms, Experimental; Mice; Organ Size; Receptors, Estrogen; Structure-Activity Relationship; Tamoxifen; Terphenyl Compounds; Uterus