Stéphane Zingue1, Julia Cisilotto2, Alain Brice Tueche3, Anupam Bishayee4, Francine Azegha Mefegue3, Louis Pergaud Sandjo2, Chantal Beatrice Magne Nde5, Evelyn Winter2, Thomas Michel6, Derek Tantoh Ndinteh7, Charline Florence Awounfack8, Kevine Kamga Silihe8, Tito Tresor Melachio Tanekou8, Tânia Beatriz Creczynski-Pasa2, Dieudonné Njamen9. 1. 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. 2. Department of Pharmaceutical Sciences, Health Sciences Centre, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil. 3. Department of Life and Earth Sciences, Higher Teachers' Training College, University of Maroua, Maroua, Cameroon. 4. Department of Pharmaceutical Sciences, College of Pharmacy, Larkin Health Sciences Institute, Miami, FL 33169, USA. 5. Hudson Institute of Medical Research, Clayton, Victoria 3168, Australia. 6. Institute of Chemistry of Nice, Faculty of Sciences, University Nice Sophia-Antipolis, UMR CNRS 7272, Valrose Park, Nice Cedex 2, France. 7. Department of Applied Chemistry, Faculty of Sciences, University of Johannesburg, Doornfontein 2028, South Africa. 8. Department of Animal Biology and Physiology, Faculty of Science, University of Yaoundé 1, Yaounde, Cameroon. 9. 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.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Crateva adansonii DC is a plant traditionally used in Cameroon to treat constipation, asthma, snakebites, postmenopausal complaints and cancers. AIM: 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. MATERIAL AND 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.
ETHNOPHARMACOLOGICAL RELEVANCE: Crateva adansonii DC is a plant traditionally used in Cameroon to treat constipation, asthma, snakebites, postmenopausal complaints and cancers. AIM: The anticancer potential of the dichloromethane/methanol extract of C. adansonii stem barks was investigated using humanbreast cancer cell and 7,12 dimethylbenz(a)anththracene (DMBA)-induced mammary tumorigenesis model in rats. MATERIAL AND 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.