Justicidin B and related lignans from two South African Monsonia species with potent activity against HeLa cervical cancer cells

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.