Cytotoxicity Effects and Apoptosis Induction by Bisbenzylisoquinoline Alkaloids fromTriclisia subcordata

Abstract

Triclisia subcordata Oliv (Menispermeaceae) is a medicinal plant traditionally used for the treatment of various diseases in West Africa. The ethanol extract of T. subcordata and its fractions were screened for in vitro anti-ovarian cancer activities using the Sulforhodamine B assay. The crude alkaloids showed the strongest activity in cell growth assays on Ovcar-8 and A2780 cell lines (IC50 < 2.4 µg/mL). A bisbenzylisoquinoline alkaloid-cycleanine was isolated using HPLC and identified by mass spectrometry and nuclear magnetic resonance analyses. The IC50 values of cycleanine and tetrandrine (an alkaloid previously reported from this plant) ranged from 7 to 14 μM on Ovcar-8, A2780, Ovcar-4, and Igrov-1 ovarian cancer cell lines. The IC50 of cycleanine on human normal ovarian surface epithelial cells was 35 ± 1 μM, hinting at modest selectivity toward cancer cells. Both cycleanine and tetrandrine caused apoptosis as shown by activation of caspases 3/7 and cleavage of poly(ADP-ribose) polymerase to form poly(ADP-ribose) polymerase-1 by using western blot analysis. Flow cytometry analyses showed that the percentages of apoptotic cells and cells in subG1 phase increased after exposure of cycleanine and tetrandrine to Ovcar-8 cells for 48 h compared with control. Cycleanine, like its isomer tetrandrine isolated from T. subcordata, could be a potential new anti-ovarian cancer agent acting through the apoptosis pathway. Copyright © 2016 John Wiley & Sons, Ltd.

Isochondodendrine and 2′-norcocsuline: additional alkaloids from Triclisia subcordata induce cytotoxicity and apoptosis in ovarian cancer cell lines

“…25 A BBIQ alkaloidcycleanine has been isolated from T. subcordata and shown to exert cytotoxicity through induction of apoptosis. 7,8 In this study two additional minor BBIQ alkaloidsisochondodendrine (2) and 2 0 -norcocsuline (3) ( Fig. 1), besides the major cycleanine (1) from T. subcordata, were isolated and characterized.…”

“…It is used for the treatment of breast cancer in Nigeria. 6 T. subcordata has been reported to possess cytotoxic, 7,8 anti-ulcer, 9 antihistamine, and antimicrobial activities. 10 Previous reports have identied some of the pharmacologically active components of T. subcordata including bisbenzylisoquinoline (BBIQ) alkaloids, tricordatine, 11 fangchinoline, 12 and tetrandrine.…”

“…15,16 We previously isolated and identied a major BBIQ alkaloidcycleanine from T. subcordata which showed in vitro antiovarian cancer activity via bioassay guided fractionation. 7,8 This study focused on isolation and structural identication of additional bioactive compounds of T. subcordata and evaluation of their in vitro cytotoxicity in ovarian cell lines by measuring their activity in cell growth and viability assays. 17 A panel of assays were used to conrm that the compounds induced apoptosis, including measurement of caspase 3/7 activity, assessing poly(ADP-ribose) polymerase (PARP) cleavage, Annexin V and propidium iodide (PI) staining.…”

A critical review: traditional uses, phytochemistry, pharmacology and toxicology of Stephania tetrandra S. Moore (Fen Fang Ji)

“…Yet compared to the positive control, paclitaxel (IC 50 values from 5 to 8 nM), anti-cancer effects on various ovarian cancer cells of cycleanine has no advantage. (Uche et al 2016). Dicentrine (39) has been shown to IC 50 values from 4 to 43 lM on different U87MG cell lines by inhibiting the over-expression of epidermal growth factor receptor cancer cells by intercalation of DNA and the introduction of DNA strand breaks.…”

A New 1,5‐Dihydroxy‐4‐methoxyisoquinoline from Scolopendra subspinipes mutilans

“…According to previous reports, the main active components of the centipede were polypeptides, histamines, quinolines, and so on . Among numerous biological active ingredients, isoquinoline alkaloid showed the strong pharmacological effects, including anticancer, antimalarial, anti‐inflammatory, antioxidant, antithrombotic, antimicrobial, and other functions …”