TY - JOUR
T1 - Justicidin B and related lignans from two South African Monsonia species with potent activity against HeLa cervical cancer cells
AU - Tajuddeen, Nasir
AU - Muyisa, Séverin
AU - Maneenet, Juthamart
AU - Nguyen, Hung Hong
AU - Naidoo-Maharaj, Dashnie
AU - Maharaj, Vinesh
AU - Awale, Suresh
AU - Bringmann, Gerhard
N1 - Publisher Copyright:
© 2023 Phytochemical Society of Europe
PY - 2024/4
Y1 - 2024/4
N2 - Cervical cancer is a deadly malignancy, one of the most common for women, evidencing the need for effective new chemotherapeutic agents to treat the disease. Lignans are widely occurring natural products with important pharmacological effects, including anticancer activities. Five arylnaphthalene lignans, isolated from Monsonia angustifolia and M. glauca (Geraniaceae), were investigated for their cytotoxicity against HeLa human cervical cancer cells. The best activity (IC50 1.2 μM) was exerted by justicidin B (4). The presence of additional methoxy groups in the “northern part” of the arylnaphthalene scaffold, at C-6 and/or C-7, lowered the cytotoxicity. Even more significantly, a free hydroxy group at C-7, leads to a drastic decrease in potency, by two orders of magnitude. Live-cell imaging experiments revealed that 4 induces changes in cancer cells morphology, effecting their elongation and eventual death. Justicidin B (4) inhibited formation of HeLa cell colonies in a dose-dependent manner. Mechanistic investigations showed that 4 modulates the expression of key proteins involved in apoptosis, suggesting that it induces cell death through several mechanisms.
AB - Cervical cancer is a deadly malignancy, one of the most common for women, evidencing the need for effective new chemotherapeutic agents to treat the disease. Lignans are widely occurring natural products with important pharmacological effects, including anticancer activities. Five arylnaphthalene lignans, isolated from Monsonia angustifolia and M. glauca (Geraniaceae), were investigated for their cytotoxicity against HeLa human cervical cancer cells. The best activity (IC50 1.2 μM) was exerted by justicidin B (4). The presence of additional methoxy groups in the “northern part” of the arylnaphthalene scaffold, at C-6 and/or C-7, lowered the cytotoxicity. Even more significantly, a free hydroxy group at C-7, leads to a drastic decrease in potency, by two orders of magnitude. Live-cell imaging experiments revealed that 4 induces changes in cancer cells morphology, effecting their elongation and eventual death. Justicidin B (4) inhibited formation of HeLa cell colonies in a dose-dependent manner. Mechanistic investigations showed that 4 modulates the expression of key proteins involved in apoptosis, suggesting that it induces cell death through several mechanisms.
KW - Anticancer
KW - Cervical cancer HeLa cells
KW - Justicidins
KW - Lignans
KW - Monsonia angustifolia
KW - Monsonia glauca
UR - http://www.scopus.com/inward/record.url?scp=85171643528&partnerID=8YFLogxK
U2 - 10.1016/j.phytol.2023.09.007
DO - 10.1016/j.phytol.2023.09.007
M3 - 学術論文
AN - SCOPUS:85171643528
SN - 1874-3900
VL - 60
SP - 234
EP - 238
JO - Phytochemistry Letters
JF - Phytochemistry Letters
ER -