Cytotoxicity of methanol extracts of Annona muricata, Passiflora edulis and nine
other Cameroonian medicinal plants towards multi-factorial drug-resistant cancer
Kuete V(1), Dzotam JK(2), Voukeng IK(2), Fankam AG(2), Efferth T(3).
(1)Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry,
University of Mainz, 55128 Mainz, Germany ; Department of Biochemistry, Faculty
of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon.
(2)Department of Biochemistry, Faculty of Science, University of Dschang, P.O.
Box 67, Dschang, Cameroon.
(3)Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry,
University of Mainz, 55128 Mainz, Germany.
BACKGROUND: Cancer cells rapidly acquire resistance leading to treatment
failures. In the present study, we have evaluated the cytotoxicity of 17 methanol
extracts from 11 Cameroonian medicinal plants against the sensitive leukemia
CCRF-CEM cells and the best ones were further tested on a panel of 8 other human
cancer cell lines, including various MDR phenotypes as well as against the normal
METHODS: The cytotoxicity of the extracts was determined using a resazurin
reduction assay meanwhile flow cytometry was used to measure cell cycle,
apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species.
RESULTS: In an initial screening using leukemia CCRF-CEM cells, ten extracts from
five plants namely Alchornea floribunda, Annona muricata, Euphorbia prostata,
Pachypodanthium staudtii and Passiflora edulis displayed IC50 values below
20 µg/mL. They were further tested in 8 other cell lines as well as in normal
AML12 hepatocytes. All selected extracts were active against leukemia CEM/ADR5000
cells with IC50 value below 40 µg/mL. IC50 values ranging from 10.13 µg/mL
(towards CEM/ADR5000 cells) to 72.01 µg/mL [towards resistant colon carcinoma
HCT116 (p53-/-) cells] for Pachypodanthium staudtii roots and from 0.11 µg/mL
(towards CCRF-CEM cells) to 108 µg/mL (towards P-glycoprotein-over-expressing
CEM/ADR5000 cells) for doxorubicin were obtained in the eight other cancer cell
lines studied. Extracts from Annona muricata leaves (AML) and seeds (AMS), and
Passiflora edulis fruit (PEF) had IC50 values below 1 µg/mL against CCRF-CEM
cells and below 10 µg/mL against its MDR subline CEM/ADR5000 cells. AML, AMS and
PEF induced MMP-loss-mediated apoptosis in CCRF-CEM cells.
CONCLUSIONS: Results of the present study suggest that some of the tested plants
namely Alchornea floribunda, Annona muricata, Euphorbia prostata, Pachypodanthium
staudtii and Passiflora edulis represent a source of anticancer drugs. Annona
muricata and Passiflora edulis are good cytotoxic plants that could be exploited
to develop phytomedicine to fight mostly hematological cancers including MDR