Crateva adansonii DC, an African ethnomedicinal plant, exerts cytotoxicity in vitro and prevents experimental mammary tumorigenesis in vivo.
BACKGROUND
Crateva adansonii DC is a plant traditionally used in Cameroon to treat constipation, asthma, snakebites, postmenopausal complaints and cancers.


OBJECTIVE
The anticancer potential of the dichloromethane/methanol extract of C. adansonii stem barks was investigated using human breast cancer cell and 7,12 dimethylbenz(a)anththracene (DMBA)-induced mammary tumorigenesis model in rats.


METHODS
The cytotoxicity of C. adansonii extract was assessed in vitro towards breast carcinoma (MCF-7 and MDA-MB-231) and non-tumoral cell lines (NIH/3T3 and HUVEC) by Alamar Blue assay. Furthermore, in vivo studies were performed on female Wistar rats treated either with C. adansonii extract at a dose of 75 or 300mg/kg body weight or with tamoxifen (3.3mg/kg body weight), starting 1 week prior DMBA treatment and lasted 12 weeks. The investigation focused on tumour burden, tumour DNA fingerprint, morphological, histological, hematological, and biochemical parameters.


RESULTS
CC50 values for the in vitro assays were 289µg/mL against MCF-7 cells and >500µg/mL in others cells, leading to a selectivity index ≥1.73. C. adansonii extract significantly (p<0.001) revealed in vivo the reduction of the cumulative tumour yield (87.23%), total tumour burden (88.64%), average tumour weight (71.11%) and tumour volume (78.07%) at the dose of 75mg/kg as compared to DMBA control group. A weak effect was also observed at 300mg/kg. This extract showed a moderate hyperplasia at the dose of 75mg/kg while at 300mg/kg no significant change was noted as compared to DMBA group. It protected rats from the DNA alteration induced by DMBA and increased antioxydant enzymes activities in mammary gland tissue homogenates. In addition, Ultra-High Performance Liquid Chromatography/ESI-QTOF-Mass Spectrometry analysis of C. adansonii extract detected structure-related of many well-known anticancer agents such as flavane gallate, flavonol, phenylpropanoïds, sesquiterpene derivatives, gallotannins and lignans. The LD50 of C. adansonii was estimated to be greater than 5000mg/kg.


CONCLUSIONS
These aforementioned results suggest that the C. adansonii extract may possess antitumor constituents, which could combat breast cancer and prevent chemically-induced breast cancer in rats.
Department of Life and Earth Sciences, Higher Teachers' Training College, University of Maroua, Maroua, Cameroon; Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, Yaounde, Cameroon; Department of Pharmaceutical Sciences, Health Sciences Centre, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil. Electronic address: stephanezingue@gmail.com.
Stéphane
S
Zingue
Department of Pharmaceutical Sciences, Health Sciences Centre, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
Julia
J
Cisilotto
Department of Life and Earth Sciences, Higher Teachers' Training College, University of Maroua, Maroua, Cameroon.
Alain Brice
AB
Tueche
Department of Pharmaceutical Sciences, College of Pharmacy, Larkin Health Sciences Institute, Miami, FL 33169, USA.
Anupam
A
Bishayee
Department of Life and Earth Sciences, Higher Teachers' Training College, University of Maroua, Maroua, Cameroon.
Francine Azegha
FA
Mefegue
Department of Pharmaceutical Sciences, Health Sciences Centre, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
Louis Pergaud
LP
Sandjo
Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia.
Chantal Beatrice
CB
Magne Nde
Department of Pharmaceutical Sciences, Health Sciences Centre, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
Evelyn
E
Winter
Institute of Chemistry of Nice, Faculty of Sciences, University Nice Sophia-Antipolis, UMR CNRS 7272, Valrose Park, Nice Cedex 2, France.
Thomas
T
Michel
Department of Applied Chemistry, Faculty of Sciences, University of Johannesburg, Doornfontein 2028, South Africa.
Derek Tantoh
DT
Ndinteh
Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, Yaounde, Cameroon.
Charline Florence
CF
Awounfack
Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, Yaounde, Cameroon.
Kevine Kamga
KK
Silihe
Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, Yaounde, Cameroon.
Tito Tresor
TT
Melachio Tanekou
Department of Pharmaceutical Sciences, Health Sciences Centre, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.
Tânia Beatriz
TB
Creczynski-Pasa
Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, Yaounde, Cameroon; Department of Applied Chemistry, Faculty of Sciences, University of Johannesburg, Doornfontein 2028, South Africa. Electronic address: dnjamen@gmail.com.
Dieudonné
D
Njamen
D015127:9,10-Dimethyl-1,2-benzanthracene; D000349:Africa; D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D031483:Capparaceae / Q000737:chemistry*; D002853:Chromatography, Liquid; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019448:Ethnobotany; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D020128:Inhibitory Concentration 50; D007928:Lethal Dose 50; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016488:Medicine, African Traditional; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D010946:Plants, Medicinal; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects
D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D013629:Tamoxifen; D015127:9,10-Dimethyl-1,2-benzanthracene
Antioxidant activity; Breast cancer; Chemoprevention; Crateva adansonii; Cytotoxicty; Dmba