In vitro screening of crude extracts and pure metabolites obtained from marine invertebrates for the treatment of breast cancer

Abstract

A total of 15 samples (crude extracts and pure secondary metabolites) obtained from marine invertebrates collected from the offshore waters of British Columbia, Papua New Guinea, and Sri Lanka have previously been shown to exert cytotoxic activity in the in vitro L1210 leukemic bioassay. We screened these metabolites for in vitro cytotoxic activity against the drug-sensitive breast-tumor cell lines MCF-7, T-47D, ZR-75-1, and MDA-MB-231; the multidrug-resistant and P-glycoprotein (Pgp)-positive breast-tumor cell lines MCF-7 Adr and MDA-A1r; and normal and malignant human breast epithelial cells (HBEC) in primary culture. Eight samples exhibited significant [drug concentration resulting in a 50% decrease in cell growth as compared with controls (ED50), less than 25 micrograms/ml] dose-dependent cytotoxicity against the drug-sensitive cell lines; the ED50 values were as low as 0.004 micrograms/ml. Five of the eight samples exhibited significant cytotoxicity against the multidrug-resistant cell lines; the ED50 values were as low as 0.0006 micrograms/ml. Incubation of MCF-7 Adr cells with varying concentrations of compounds in the presence of Adriamycin demonstrated that none of the compounds tested interfered with Pgp function. Results obtained using HBEC in primary culture showed a wide range of chemosensitivities for a given drug against tissue taken from different patients, demonstrating the uniqueness of the response of different individuals to chemotherapy.

Synthesis and Biological Evaluation of Modified Miuraenamides

“…Jasplakinolide was found to initiate actin polymerization and stabilizes already formed actin microfilaments, which causes significant morphological changes in the cell . The same effects were also observed for the geodiamolides . Interestingly, geodiamolide H showed cytotoxic effects towards a range of tumor cell lines, while geodiamolide I was inactive .…”

Synthesis and Biological Evaluation of Modified Miuraenamides

“…Jasplakinolide was found to initiate actin polymerization and stabilizes already formed actin microfilaments, which causes significant morphological changes in the cell . The same effects were also observed for the geodiamolides . Interestingly, geodiamolide H showed cytotoxic effects towards a range of tumor cell lines, while geodiamolide I was inactive .…”

New Geodiamolides from the Sponge Cymbastela sp. Collected in Papua New Guinea

“…The upfield shift of H-17 from δ 7.45 in geodiamolide G (8) to δ 7.25 in 11 and to δ 7.12 in 12 was analogous to the observed changes in the chemical shift of H-17 in geodiamolides B (3) and C (4) relative to geodiamolide A (2), where the C-18 substituent varies from iodine in 2 to bromine in 3 and chlorine in 4. 3,4 Thus, geodiamolides J (11) and K (12) were the C-18 bromo and chloro analogues of geodiamolide G (8), respectively.…”

“…was recollected from the original dive sites at Motupore and Madang in Papua New Guinea. Bioassay-guided fractionation of extracts from the recollected Cymbastela specimens led to the isolation of hemiasterlins and criamides, 5 the known geodiamolides A-G (2-8), [3][4][5] and the novel geodiamolides J-P (11)(12)(13)(14)(15)(16)(17) 1) revealed that the resonances for the alaninepolyketide-alanine portions of the molecules (H-1 to H-8, H-12 to H-20, H-22 to H-25, and H-27) were identical, and the only significant difference was observed in the chemical shifts of the resonances assigned to H-17 in the tyrosine residue. The upfield shift of H-17 from δ 7.45 in geodiamolide G (8) to δ 7.25 in 11 and to δ 7.12 in 12 was analogous to the observed changes in the chemical shift of H-17 in geodiamolides B (3) and C (4) relative to geodiamolide A (2), where the C-18 substituent varies from iodine in 2 to bromine in 3 and chlorine in 4.…”

“…5 This recollected Cymbastela sp. sample also yielded small amounts of eight new cyclic depsipetides, geodiamolides J-P (11)(12)(13)(14)(15)(16)(17), and R (19), whose structures are reported herein. Geodiamolides L-P (13)(14)(15)(16)(17) and R (19) represent the first examples in this class of compounds in which a serine residue has been incorporated into the structure (Chart 1).…”

THz irradiation inhibits cell division by affecting actin dynamics

“…Jasplakinolide, a naturally occurring cyclic peptide from the marine sponge Jaspis sp [54], is a membranepermeable, actin-polymerizing, and filament-stabilizing drug [55]. Jasplakinolide has a wide range of known biological functions, which include antifungal and antitumor activities [56][57][58]. Thus, by analogy with jasplakinolide, we suggest that THz irradiation can be used to manipulate cell functions via actin polymerization.…”

Synthesis and Biological Evaluation of Modified Miuraenamides

“…Jasplakinolide was found to initiate actin polymerization and stabilizes already formed actin microfilaments, which causes significant morphological changes in the cell . The same effects were also observed for the geodiamolides . Interestingly, geodiamolide H showed cytotoxic effects towards a range of tumor cell lines, while geodiamolide I was inactive .…”

New Geodiamolides from the Sponge Cymbastela sp. Collected in Papua New Guinea

“…The upfield shift of H-17 from δ 7.45 in geodiamolide G (8) to δ 7.25 in 11 and to δ 7.12 in 12 was analogous to the observed changes in the chemical shift of H-17 in geodiamolides B (3) and C (4) relative to geodiamolide A (2), where the C-18 substituent varies from iodine in 2 to bromine in 3 and chlorine in 4. 3,4 Thus, geodiamolides J (11) and K (12) were the C-18 bromo and chloro analogues of geodiamolide G (8), respectively.…”

“…was recollected from the original dive sites at Motupore and Madang in Papua New Guinea. Bioassay-guided fractionation of extracts from the recollected Cymbastela specimens led to the isolation of hemiasterlins and criamides, 5 the known geodiamolides A-G (2-8), [3][4][5] and the novel geodiamolides J-P (11)(12)(13)(14)(15)(16)(17) 1) revealed that the resonances for the alaninepolyketide-alanine portions of the molecules (H-1 to H-8, H-12 to H-20, H-22 to H-25, and H-27) were identical, and the only significant difference was observed in the chemical shifts of the resonances assigned to H-17 in the tyrosine residue. The upfield shift of H-17 from δ 7.45 in geodiamolide G (8) to δ 7.25 in 11 and to δ 7.12 in 12 was analogous to the observed changes in the chemical shift of H-17 in geodiamolides B (3) and C (4) relative to geodiamolide A (2), where the C-18 substituent varies from iodine in 2 to bromine in 3 and chlorine in 4.…”

“…5 This recollected Cymbastela sp. sample also yielded small amounts of eight new cyclic depsipetides, geodiamolides J-P (11)(12)(13)(14)(15)(16)(17), and R (19), whose structures are reported herein. Geodiamolides L-P (13)(14)(15)(16)(17) and R (19) represent the first examples in this class of compounds in which a serine residue has been incorporated into the structure (Chart 1).…”

THz irradiation inhibits cell division by affecting actin dynamics

“…Jasplakinolide, a naturally occurring cyclic peptide from the marine sponge Jaspis sp [54], is a membranepermeable, actin-polymerizing, and filament-stabilizing drug [55]. Jasplakinolide has a wide range of known biological functions, which include antifungal and antitumor activities [56][57][58]. Thus, by analogy with jasplakinolide, we suggest that THz irradiation can be used to manipulate cell functions via actin polymerization.…”

Synthesis and Biological Evaluation of Modified Miuraenamides

“…Jasplakinolide was found to initiate actin polymerization and stabilizes already formed actin microfilaments, which causes significant morphological changes in the cell . The same effects were also observed for the geodiamolides . Interestingly, geodiamolide H showed cytotoxic effects towards a range of tumor cell lines, while geodiamolide I was inactive .…”

New Geodiamolides from the Sponge Cymbastela sp. Collected in Papua New Guinea

“…The upfield shift of H-17 from δ 7.45 in geodiamolide G (8) to δ 7.25 in 11 and to δ 7.12 in 12 was analogous to the observed changes in the chemical shift of H-17 in geodiamolides B (3) and C (4) relative to geodiamolide A (2), where the C-18 substituent varies from iodine in 2 to bromine in 3 and chlorine in 4. 3,4 Thus, geodiamolides J (11) and K (12) were the C-18 bromo and chloro analogues of geodiamolide G (8), respectively.…”

“…was recollected from the original dive sites at Motupore and Madang in Papua New Guinea. Bioassay-guided fractionation of extracts from the recollected Cymbastela specimens led to the isolation of hemiasterlins and criamides, 5 the known geodiamolides A-G (2-8), [3][4][5] and the novel geodiamolides J-P (11)(12)(13)(14)(15)(16)(17) 1) revealed that the resonances for the alaninepolyketide-alanine portions of the molecules (H-1 to H-8, H-12 to H-20, H-22 to H-25, and H-27) were identical, and the only significant difference was observed in the chemical shifts of the resonances assigned to H-17 in the tyrosine residue. The upfield shift of H-17 from δ 7.45 in geodiamolide G (8) to δ 7.25 in 11 and to δ 7.12 in 12 was analogous to the observed changes in the chemical shift of H-17 in geodiamolides B (3) and C (4) relative to geodiamolide A (2), where the C-18 substituent varies from iodine in 2 to bromine in 3 and chlorine in 4.…”

“…5 This recollected Cymbastela sp. sample also yielded small amounts of eight new cyclic depsipetides, geodiamolides J-P (11)(12)(13)(14)(15)(16)(17), and R (19), whose structures are reported herein. Geodiamolides L-P (13)(14)(15)(16)(17) and R (19) represent the first examples in this class of compounds in which a serine residue has been incorporated into the structure (Chart 1).…”

THz irradiation inhibits cell division by affecting actin dynamics

“…Jasplakinolide, a naturally occurring cyclic peptide from the marine sponge Jaspis sp [54], is a membranepermeable, actin-polymerizing, and filament-stabilizing drug [55]. Jasplakinolide has a wide range of known biological functions, which include antifungal and antitumor activities [56][57][58]. Thus, by analogy with jasplakinolide, we suggest that THz irradiation can be used to manipulate cell functions via actin polymerization.…”