Cytotoxic and Anti-Plasmodial Activities of Stephania dielsiana Y.C. Wu Extracts and the Isolated Compounds

Abstract

Natural products remain a viable source of novel therapeutics, and as detection and extraction techniques improve, we can identify more molecules from a broader set of plant tissues. The aim of this study was an investigation of the cytotoxic and anti-plasmodial activities of the methanol extract from Stephania dielsiana Y.C. Wu leaves and its isolated compounds. Our study led to the isolation of seven alkaloids, among which oxostephanine (1) is the most active against several cancer cell lines including HeLa, MDA-MB231, MDA-MB-468, MCF-7, and non-cancer cell lines, such as 184B5 and MCF10A, with IC50 values ranging from 1.66 to 4.35 μM. Morever, oxostephanine (1) is on average two-fold more active against cancer cells than stephanine (3), having a similar chemical structure. Cells treated with oxostephanine (1) are arrested at G2/M cell cycle, followed by the formation of aneuploidy and apoptotic cell death. The G2/M arrest appears to be due, at least in part, to the inactivation of Aurora kinases, which is implicated in the onset and progression of many forms of human cancer. An in-silico molecular modeling study suggests that oxostephanine (1) binds to the ATP binding pocket of Aurora kinases to inactivate their activities. Unlike oxostephanine (1), thailandine (2) is highly effective against only the triple-negative MDA-MB-468 breast cancer cells. However, it showed excellent selectivity against the cancer cell line when compared to its effects on non-cancer cells. Furthermore, thailandine (2) showed excellent anti-plasmodial activity against both chloroquine-susceptible 3D7 and chloroquine-resistant W2 Plasmodium falciparum strains. The structure–activity relationship of isolated compound was also discussed in this study. The results of this study support the traditional use of Stephania dielsiana Y.C. Wu and the lead molecules identified can be further optimized for the development of highly effective and safe anti-cancer and anti-plasmodial drugs.

Dual roles of oxostephanine as an Aurora kinase inhibitor and angiogenesis suppressor

“…Moreover, as shown by immunofluorescence assay, both compounds downregulated the phosphorylation of protein histone H3 at serine 10 in cancer cells. These data are consistent with those of the study by Knockleby et al ( 23 ), demonstrating that oxostephanine inhibited H3S10ph in HeLa cells ( 23 ). As the phosphorylation of histone H3 at serine 10 is considered a marker of activated Aurora B kinase ( 7 , 8 ), hence oxostephanine could prevent the function of this kinase.…”

“…Apoptosis induction is a characteristic of Aurora kinase inhibitors ( 18 , 23 ). Hence, the present study examined whether oxostephanine could induce the apoptosis of OVCAR-8 cancer cells.…”

“…SD10/2019) has been deposited at the Department of Botany and Pharmacognosy, Vietnam University of Traditional Medicine, Hanoi, Vietnam. The process used for the isolation and characterization of oxostephanine from the leaves of S. dielsiana in Vietnam has been previously published ( 22 , 23 ). In brief, the leaves of S. dielsiana (7 kg) were extracted with 95% MeOH (3×15 liters, 3 days each) at room temperature.…”

“…In addition, oxostephanine has been shown to exhibit potent activity against breast cancer cells and MOLT-3 acute lymphoblastic leukemia cells ( 21 ). Moreover, Knockleby et al ( 23 ) revealed that oxostephanine inhibited the activity of Aurora kinase A and B by the competition of ATP binding sites in an in vitro kinase assay.…”

Arthropod-Borne Disease Control at a Glance: What’s New on Drug Development?

“…To our eyes, these studies represent key research advances regarding the development of drugs for the control of ABD. Furthermore, recent reviews providing well-updated scenarios about drug development against selected ABD and formulating new research challenges are outlined [14][15][16][17][18][19][20][21][22][23]. Among key ABD, major focuses have been malaria, Chagas disease, dengue, human African trypanosomiasis (HAT), leishmaniasis, and Zika.…”