ABSTRACT
Euphorbia kansui is a commonly used traditional Chinese medicine for the treatment of edema, pleural effusion, and asthma, etc. According to the previous researches, terpenoids in E. kansui possess various biological activities, e.g., anti-virus, anti-allergy, antitumor effects. In this work, twenty five terpenoids were isolated from E. kansui, including thirteen ingenane- and eight jatrophane-type diterpenoids (with two new compounds, kansuinin P and Q) and four triterpenoids. Eighteen of them were analyzed by MTS assay for in vitro anticancer activity in five human cancer cell lines. Structure-activity relationship for 12 ingenane-type diterpenoids in colorectal cancer Colo205 cells were preliminary studied. Significant anti-proliferation activities were observed in human melanoma cells breast cancer MDA-MB-435 cells and Colo205 cells. More than half of the isolated ingenane-type diterpenoids showed inhibitory activities in MDA-MB-435 cells. Eight ingenane- and one jatrophane-type diterpenoids possessed much lower IC values in MDA-MB-435 cells than positive control staurosporine. Preliminary structure-activity relationship analysis showed that substituent on position 20 was important for the activity of ingenane-type diterpenoids in Colo205 cells and substituent on position 3 contributed more significant biological activity of the compounds than that on position 5 in both MDA-MB-435 and Colo205 cells.
Subject(s)
Humans , Cell Line, Tumor , Cell Proliferation , Drugs, Chinese Herbal , Chemistry , Pharmacology , Euphorbia , Chemistry , Molecular Structure , Neoplasms , Drug Therapy , Structure-Activity Relationship , Terpenes , Chemistry , PharmacologyABSTRACT
In vitro cytotoxic potential of extracts (95% and 50% ethanolic extract and hot water extract at concentration of 100 µg/ml) from leaves of Holarrhena antidysenterica was evaluated against fourteen human cancer cell lines — A-549, COLO-205, DU-145, HeLa, HEP-2, IMR-32, KB, MCF-7, NCI-H23, OVCAR-5, SiHa, SK-N-MC, SW-620 and ZR-75-1 from nine different tissues (breast, colon, cervix, CNS, lung, liver, oral, ovary and prostate) using SRB assay. The 95% ethanolic extract displayed maximum anti-proliferative effect in the range of 73-92% against eight human cancer cell lines, while 50% ethanolic extract showed cytotoxic activity in the range of 70-94% against seven human cancer cell lines. However, the hot water extract did not show any activity. Among the fractions of 95% and 50% ethanolic extract, significant cytotoxic activity was found in the chloroform soluble fraction of 95% ethanolic extract at 100 µg/ml; it inhibited the growth in the range of 71-99% of seven human cancer cell lines from five different tissues viz., OVCAR-5 (ovary), HT-29 (colon), SK-N-MC (neuroblastoma), HEP-2 (liver), COLO-205 (colon), NIH-OVCAR-3 (ovary) and A-549 (lung). The cytotoxic activity of chloroform soluble fraction was found to be higher than 5-flurouracil, adriamycin, mitomycin-c and paclitaxel (anticancer drugs used as positive controls). Further in vivo studies and identification of active components from the chloroform fraction and their exact mechanism of action could be useful in designing new anticancer therapeutic agents.
Subject(s)
Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Holarrhena/chemistry , Humans , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Plant Leaves/chemistryABSTRACT
The anti-proliferative efficacy of t,t-conjugated linoleic acid (t,t-CLA), c9,t11-CLA, and t10,c12-CLA was compared in several human cancer cell lines. Gastric NCI-N87, liver Hep3B, pancreas Capan-2, and lung NCI-H522 cancer cells were incubated with 50 microM CLA isomers over a period of 6 days. The t,t-CLA inhibited the growth of all cancer cell lines to different extents, but c9,t11-CLA and t10,c12-CLA inhibited or stimulated the growth of the cancer cell lines. NCI-N87 cells were the most sensitive to growth inhibition and apoptosis from all CLA isomers tested. In NCI-N87 cells, CLA isomers reduced the release of arachidonic acid (AA) via the inhibition of cytosolic phospholipase A2 (cPLA2) activity, consequently reducing the production of PGE2 through the inhibition of cyclooxygenase-2 (COX-2). The efficacies of CLA isomers were in the following order (from most to least effective): t,t-CLA, t10,c12-CLA and c9,t11-CLA. Overall, these results imply that the anti-proliferative efficacy of t,t-CLA on cancer cells, especially NCI-N87 cells, was greater than other CLA isomers due to its induction of apoptosis through the inhibition of cPLA2 and COX-2 activities.