Molecular Activities and Mechanisms of Action of Substances and Molecules from Medicinal Plants from Sub-Saharan Africa on Prostate and Cervical Cancer Cells.

BACKGROUND: Despite years of medical research, cancer remains a major public health problem worldwide, particularly in Africa. The cost, duration, and toxicity of currently available treatments are all drawbacks. Plant secondary metabolites are significant anticancer compounds. Already used in traditional health systems, plants are currently the subject of numerous studies to discover new anti-cancer drugs. OBJECTIVE: This review assesses the literature on the cytotoxic effect of plant substances (extracts) and molecules on prostate and cervical cancer cell lines. METHOD: PubMed, Science Direct, and Google Scholar were used to find in vitro studies carried out between 2006 and 2023 related to the cytotoxicity of extracts, substances and/or molecules from plants harvested in sub-Saharan Africa against prostate and/or cervical cancer cell lines. RESULTS: A total of 36 reports on the cytotoxic potential of 96 medicinal plants from sub-Saharan Africa were extracted from the selected databases. All the plants listed had a cytotoxic effect on prostate and/or cervical cancer cells. Some plant extracts or molecules showed significant activity with an IC50< 20 µg/ml. Burkina Faso and South Africa had the most plant extracts tested for prostate and cervical cancer, respectively. CONCLUSION: A total of 36 reports on the cytotoxic potential of 96 medicinal plants from sub-Saharan Africa were extracted from the selected databases.

In vitro activities and mechanisms of action of anti-cancer molecules from African medicinal plants: a systematic review.

Cancer is one of the leading causes of death worldwide. In recent years, African countries have been faced with a rapid increase in morbidity and mortality due to this pathology. Management is often complicated by the high treatment costs, side effects and the increasing occurrence of resistance to treatments. The identification of new active ingredients extracted from endemic medicinal plants is definitively an interesting approach for the implementation of new therapeutic strategies: their extraction is often lower cost; their identification is based on an ethnobotanical history and a tradipratic approach; their use by low-income populations is simpler; this can help in the development of new synthetic molecules that are more active, more effective and with fewer side effects. The objective of this review is to document the molecules derived from African medicinal plants whose in vitro anti-cancer activities and the mechanisms of molecular actions have been identified. From the scientific databases Science Direct, PubMed and Google Scholar, we searched for publications on compounds isolated from African medicinal plants and having activity on cancer cells in culture. The data were analyzed in particular with regard to the cytotoxicity of the compounds and their mode of action. A total of 90 compounds of these African medicinal plants were selected. They come from nine chemical groups: alkaloids, flavonoids, polyphenols, quinones, saponins, steroids, terpenoids, xanthones and organic sulfides. These compounds have been associated with several cellular effects: i) Cytotoxicity, including caspase activation, alteration of mitochondrial membrane potential, and/or induction of reactive oxygen species (ROS); ii) Anti-angiogenesis; iii) Anti-metastatic properties. This review points out that the cited African plants are rich in active ingredients with anticancer properties. It also stresses that screening of these anti-tumor active ingredients should be continued at the continental scale. Altogether, this work provides a rational basis for the selection of phytochemical compounds for use in clinical trials.

Contribution of Sub-Saharan African medicinal plants to cancer research: Scientific basis 2013-2023.

Cancer incidence and mortality rates are increasing worldwide. Cancer treatment remains a real challenge for African countries, especially in sub-Saharan Africa where funding and resources are very limited. High costs, side effects and drug resistance associated with cancer treatment have encouraged scientists to invest in research into new herbal cancer drugs. In order to identify potential anticancer plants for drug development, this review aims to collect and summarize anticancer activities (in vitro/in vivo) and molecular mechanisms of sub-Saharan African medicinal plant extracts against cancer cell lines. Scientific databases such as ScienceDirect, Google Scholar and PubMed were used to search for research articles published from January 2013 to May 2023 on anticancer medicinal plants in sub-Saharan Africa. The data were analyzed to highlight the cytotoxicity and molecular mechanisms of action of these listed plants. A total of 85 research papers covering 204 medicinal plant species were selected for this review. These plants come from 57 families, the most dominant being the plants of the family Amaryllidaceae (16), Fabaceae (14), Annonaceae (10), Asteraceae (10). Plant extracts exert their anticancer activity mainly by inducing apoptosis and stopping the cell cycle of cancer cells. Several plant extracts from sub-Saharan Africa therefore have strong potential for the search for original anticancer phytochemicals. Chemoproteomics, multi-omics, genetic editing technology (CRISPR/Cas9), combined therapies and artificial intelligence tools are cutting edge emerging technologies that facilitate the discovery and structural understanding of anticancer molecules of medicinal plants, reveal their direct targets, explore their therapeutic uses and molecular bases.

Chemical Composition of Essential Oil of Cymbopogon schoenanthus (L.) Spreng from Burkina Faso, and Effects against Prostate and Cervical Cancer Cell Lines.

The aim of this research was to evaluate the essential oil of Cymbopogon schoenanthus (L.) Spreng. (C. schoenanthus) from Burkina Faso in terms of cytotoxic activity against LNCaP cells, derived from prostate cancer, and HeLa cells, derived from cervical cancer. Antioxidant activities were evaluated in vitro. Essential oil (EO) was extracted by hydrodistillation and analyzed by GC/FID and GC/MS. Thirty-seven compounds were identified, the major compounds being piperitone (49.9%), δ-2-carene (24.02%), elemol (5.79%) and limonene (4.31%). EO exhibited a poor antioxidant activity, as shown by the inhibition of DPPH radicals (IC50 = 1730 ± 80 µg/mL) and ABTS+. (IC50 = 2890 ± 26.9 µg/mL). Conversely, EO decreased the proliferation of LNCaP and HeLa cells with respective IC50 values of 135.53 ± 5.27 µg/mL and 146.17 ± 11 µg/mL. EO also prevented LNCaP cell migration and led to the arrest of their cell cycle in the G2/M phase. Altogether, this work points out for the first time that EO of C. schoenanthus from Burkina Faso could be an effective natural anticancer agent.

Involvement of ERCC1 (rs3212986) and ERCC2 (rs1799793, rs13181) polymorphisms of DNA repair genes in breast cancer occurrence in Burkina Faso.

BACKGROUND: Genetic alterations can result in DNA repair defects, increasing susceptibility to breast cancer. The aim of this study was to evaluate the involvement of two DNA repair genes, ERCC1 (rs3212986, GenBank NC_000073.9) and ERCC2 (rs1799793, rs13181, GenBank: NC_000019.10) in the occurrence of breast cancer in Burkina Faso. METHODS: This case-control study enrolled 128 participants including 64 patients and 64 healthy controls. Genotyping of polymorphisms were performed by real-time PCR and PCR-RFLP. RESULTS: The heterozygous AC genotype of the ERCC2rs13181 polymorphism was associated with the occurrence of breast cancer when the mutant allele is inherited under the dominant pattern (CC/AC vs AA; OR = 2.74, 95% IC (1.09-6.87); p = .028), but this association became insignificant after the Bonferroni correction (p = .156). No association was observed between ERCC1rs3212986 and ERCC2rs1799793 polymorphisms and breast cancer risk. CONCLUSION: This study showed that the heterozygous genotype (CA) of the ERCC2rs13181 polymorphism may be associated with a risk of breast cancer.

KIR2DL2, KIR2DL5A and KIR2DL5B Genes Induce Susceptibility to Dengue Virus Infection, while KIR3DL3 and KIR2DS5 Confer Protection.

Background and Objectives: Dengue fever (DF), an emerging and re-emerging viral disease, is a major public health problem. The aim of this study was to investigate the influence of KIRs genes polymorphism and KIRs genotypes in susceptibility to dengue virus infection and disease severity in a population from Burkina Faso through a case-control study. Methods: KIRs genes determination was performed using PCR-SSP in 50 patients infected by dengue virus (DENV) and 54 Healthy controls (HC) subjects who had never been infected. Results: Data analysis showed significant association between frequencies of three KIR genes and dengue virus infection (DF): KIR2DL2 (OR: 7.32; IC: 2.87-18.65; P < 0.001); KIR2DL5A (OR: 15.00, IC: 5.68-39.59; P < 0.001) and KIR2DL5B (OR: 11.43; IC: 4.42-29; P < 0.001). While, KIR3DL3 (OR: 0.13, IC: 0.052-0.32; P < 0.001) and KIR2DS5 (OR: 0.12; IC: 0.04-0.30; P < 0.001) were associated with protection against DF. KIR2DL4 (OR: 9.75; IC95%: 1.33-70.97; p: 0.03) and KIRD3DL1 (OR: 12.00; IC95%: 1.60-90.13; p: 0.02) were associated with an increased risk in the development of secondary dengue infection (SDI). Conclusion: The results suggest a contribution of KIR2DL2, KIR2DL5A, and KIR2DL5B genes in the susceptibility of DF development. In contrast, KIR3DL3 and KIR2DS5 were associated with protection against DF development by enhancing both innate and acquired immune responses.

Mutations in exon 11 (11.1 and 11.2) of the BRCA1 gene and risk factors for breast cancer in Burkina Faso.

Breast cancer is the leading cause of death among women in both developed and developing countries. It is multifactorial, including genetic predispositions such as oncogenic mutations on BRCA1 and 2 genes. The objectives of the present study were to identify oncogenic mutations in exon 11 of the BRCA1 gene and to determine the risk factors for breast cancer among women population in Burkina Faso. This study involved 100 women, including 50 cases of breast cancer and 50 controls (no clinical signs and no family history of breast cancer or other cancers). Mutations in the BRCA1 gene were detected by PCR using sequence primers specific for exon 11 fragments (11.1 and 11.2). In our study population, age (OR=22.40; CI: 4.33-115.82; p<0.001) and obesity (OR=4.23; CI: 1.64-10.92; p=0.003) were risk factors while multiparity was a protective factor for breast cancer (OR=0.35; CI: 0.15-0.81; p=0.02). A mutation was found on both fragments 11.1 and 11.2 of the BRCA1 gene exon 11 in 04/50 (8.0 %) of patients. No mutations were observed in controls. The present study revealed high frequency of oncogenic mutations in exon 11 fragments (11.1 and 11.2) of the BRCA1 gene. These mutations on exon 11 are and involved in the occurrence of breast cancer in our population. Age and obesity were also risk factors for breast cancer among women population in Burkina Faso.

Effects of extracts and molecules derived from medicinal plants of West Africa in the prevention and treatment of gynecological cancers. A Review.

Medicinal plants are a potential source of drug discovery and development of new pharmacological compounds for cancer chemoprevention. More than 80% of the West African population uses medicinal plants. It is estimated that over 60% of approved anti-cancer agents are derived from plants. The plant raw material used in African traditional medicine and particularly in West Africa can be an important source for the research of anti-tumor drugs against gynecological cancers. These tumors have a negative impact on women's general health status and causes enormous health costs as they affect all age groups. Gynecological cancers remain thus a major concern worldwide, especially in West Africa where these cancers are the leading cause of cancer deaths in women. This review reports on the contribution of West African flora to the discovery of potential antiproliferative and/or cytotoxic phytochemical compounds against gynecological cancer cells. Scientific databases such as PubMed, ScienceDirect, Scopus and GoogleScholar were used to extract publications reporting West African plants and/or isolated compounds used in cell models of gynecological cancers. Thresholds of cytotoxicity and modes of action of these phytochemicals have been summarized. This research can serve as a basis for taking medicinal plants into account in the management of these gynecological cancers in resource-limited countries such as those in West Africa.

Chemical Composition, Antioxidant and Cytotoxic Activities of Hyptis suaveolens (L.) Poit. Essential Oil on Prostate and Cervical Cancers Cells.

BACKGROUND AND OBJECTIVE: Hyptis suaveolens is an aromatic plant used in traditional medicine in Burkina Faso for management of various diseases including wounds and inflammatory diseases. Thus, the objective of this work was to characterize the chemical composition, antioxidant and cytotoxic activity of Essential Oil (EO) of H. suaveolens from Burkina Faso on cultured cancer cells. MATERIALS AND METHODS: The chemical composition of EO was determined by GC/FID and GC/MS analysis and the antioxidant activity was evaluated through inhibition of DPPH radicals and ABTS +• radical cations. The cytotoxic activity in prostate cancer cells (LNCaP) and cervical cancer cells (HeLa) of EO was evaluated by MTT assay and effect on cells cycle by flow cytometry analysis. RESULTS: A total of 58 compounds were identified in the EO of H. suaveolens of which the major compounds identified are Sabinene 14.03%, ß-Pinene 5.92%, Limonene 4.40%, Eucalyptol 12.78%, Trans-Oxide of Linalol 5.43%, ß-Caryophyllene 11.27%, Germacrene-D 3.04% and Bicyclogermacrene 8.08%. The EO of H. suaveolens showed antioxidant activity and concentration dependent antiproliferative activities with G0/G1 arrest on LNCaP and HeLa cells. CONCLUSIONS: This work help to justify some uses of H. suaveolens in traditional medicine in Burkina Faso and also, presents a promising new application for the essential oil of H. suaveolens in prostate and cervical cancer research.

Pharmacological Modulation of Steroid Activity in Hormone-Dependent Breast and Prostate Cancers: Effect of Some Plant Extract Derivatives.

: The great majority of breast and prostate tumors are hormone-dependent cancers; hence, estrogens and androgens can, respectively, drive their developments, making it possible to use pharmacological therapies in their hormone-dependent phases by targeting the levels of steroid or modulating their physiological activity through their respective nuclear receptors when the tumors relapse. Unfortunately, at some stage, both breast and prostate cancers become resistant to pharmacological treatments that aim to block their receptors, estrogen (ER) or androgen (AR) receptors, respectively. So far, antiestrogens and antiandrogens used in clinics have been designed based on their structural analogies with natural hormones, 17-ß estradiol and dihydrotestosterone. Plants are a potential source of drug discovery and the development of new pharmacological compounds. The aim of this review article is to highlight the recent advances in the pharmacological modulation of androgen or estrogen levels, and their activity through their cognate nuclear receptors in prostate or breast cancer and the effects of some plants extracts.

Chemical composition, antioxidant, anti-inflammatory and antiproliferative activities of the essential oil of Cymbopogon nardus, a plant used in traditional medicine.

Objectives Natural products commonly used in traditional medicine, such as essential oils (EOs), are attractive sources for the development of molecules with anti-proliferative activities for future treatment of human cancers, e.g., prostate and cervical cancer. In this study, the chemical composition of the EO from Cymbopogon nardus was characterized, as well as its antioxidativeproperties and anti-inflammatory and antiproliferative activities on LNCaP cells derived from prostate cancer. Methods The chemical composition of the EO was determined by GC/FID and GC/MS analyses. The antioxidative properties were assessed using DPPH radical scavenging assay and ABTS+• radical cation decolorization assay, and the anti-inflammatory capacity was determined by the inhibition of the lipoxygenase activity. Antiproliferative activity was evaluated by MTT assay. Results Collectively, our data show that the major constituents of C. nardus EO are citronellal (33.06 %), geraniol (28.40 %), nerol (10.94 %), elemol (5.25 %) and delta-elemene (4.09 %). C. nardus EO shows modest antioxidant and anti-inflammatory activity compared to the standard galic acid. C. nardus EO exhibits the best antiproliferative activity on the prostate cancer cell line LNCaP with an IC50 of 58.0 ± 7.9 µg/mL, acting through the induction of the cell cycle arrest. Conclusions This study has determined that C. nardus EO efficiently triggers cytotoxicity and pens a new field of investigation regarding the putative use of this EO in vivo.

Cymbopogon citratus and Cymbopogon giganteus essential oils have cytotoxic effects on tumor cell cultures. Identification of citral as a new putative anti-proliferative molecule.

Cymbopogon species are used as traditional remedies in Burkina Faso for treating several diseases. We aimed to study the effects of their essential oils on cancer cell lines. For that purpose, Cymbopogon citratus (DC.) Stapf. and Cymbopogon giganteus Chiov. were studied for their essential oils after various chemical extractions. Antioxidant, potential anti-inflammatory action (inhibition of lipoxygenase) and cytotoxic activities were also tested on various prostate cancer and glioblastoma cell lines. Thirty-three compounds were identified in the essential oil of C. giganteus: Limonene (19.33%), Mentha-1(7),8-dien-2-ol cis (17.34%), Mentha-1(7),8-dien-2-ol trans (13.95%), trans-Mentha-2,8-diene-para-ol 1 (13.91%) and Mentha-2,8-diene-1-ol, cis-para (8.10%) were the most abundant. C. citratus essential oil contained 15 compounds and the major ones were geranial/citral A (48.18%) and neral/citral B (34.37%). Essential oil of C. citratus showed the highest ability to scavenge DPPH+ radicals (approximately 68% at 8 mg/mL) while C. giganteus exhibited the highest capability to reduce ABTS+ (0.59µmolET/g). The essential oil of C. citratus was the most effective on prostate cell lines LNCaP (IC50 = 6.36 µg/ml) and PC-3 (IC50 = 32.1 µg/ml), and on glioblastoma cell lines (SF-767 (IC50 = 45.13 µg/ml) and SF-763 (IC50 = 172.05 µg/ml). Interestingly, the activity of essential oil of C. citratus was statistically equal to that of its major component, citral. Combination of both oils showed antagonist, additive, indifferent and synergistic effects on LNCaP, PC-3, SF-767 and SF-763 cell lines, respectively. In conclusion, plants from the traditional medicine in Burkina Faso could be of interest for identifying new compounds, such as citral, for the treatment of prostate cancer and glioblastoma.

Lipid Homeostasis and Ligands for Liver X Receptors: Identification and Characterization.

Screening of bona fide ligands for nuclear receptors is a real tour de force as the identified molecules are supposed to be able to activate the targeted proteins in cell culture as well as in vivo. Indeed orphan nuclear receptors are putative pharmacologically targets for various diseases. It is thus necessary to have quick and reproductive systems that help in identifying new ligands, agonist or antagonist, before using them in vivo in animal models to check for secondary effects. Here, we describe the transient transfections (homologous and heterologous) used for the screening of ligands for liver X receptor α (LXRα, NR1H3) in HeLa cells.

Anticancer activity of essential oils and their chemical components - a review.

Essential oils are widely used in pharmaceutical, sanitary, cosmetic, agriculture and food industries for their bactericidal, virucidal, fungicidal, antiparasitical and insecticidal properties. Their anticancer activity is well documented. Over a hundred essential oils from more than twenty plant families have been tested on more than twenty types of cancers in last past ten years. This review is focused on the activity of essential oils and their components on various types of cancers. For some of them the mechanisms involved in their anticancer activities have been carried out.

Chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils of plants from Burkina Faso.

This research highlights the chemical composition, antioxidant, anti-inflammatory and anti-proliferative activities of essential oils from leaves of Ocimum basilicum, Ocimum americanum, Hyptis spicigera, Lippia multiflora, Ageratum conyzoides, Eucalyptus camaldulensis and Zingiber officinale. Essential oils were analyzed by gas chromatography-mass spectrometry and gas chromatography-flame ionization detector. Major constituents were α-terpineol (59.78%) and ß-caryophyllene (10.54%) for Ocimum basilicum; 1, 8-cineol (31.22%), camphor (12.730%), α-pinene (6.87%) and trans α-bergamotene (5.32%) for Ocimum americanum; ß-caryophyllene (21%), α-pinene (20.11%), sabinene (10.26%), ß-pinene (9.22%) and α-phellandrene (7.03%) for Hyptis spicigera; p-cymene (25.27%), ß-caryophyllene (12.70%), thymol (11.88), γ-terpinene (9.17%) and thymyle acetate (7.64%) for Lippia multiflora; precocene (82.10%)for Ageratum conyzoides; eucalyptol (59.55%), α-pinene (9.17%) and limonene (8.76%) for Eucalyptus camaldulensis; arcurcumene (16.67%), camphene (12.70%), zingiberene (8.40%), ß-bisabolene (7.83%) and ß-sesquiphellandrène (5.34%) for Zingiber officinale. Antioxidant activities were examined using 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) methods. O. basilicum and L. multiflora exhibited the highest antioxidant activity in DPPH and ABTS tests, respectively. Anti-inflammatory properties were evaluated by measuring the inhibition of lipoxygenase activity and essential oil of Z. officinale was the most active. Anti-proliferative effect was assayed by the measurement of MTT on LNCaP and PC-3 prostate cancer cell lines, and SF-763 and SF-767 glioblastoma cell lines. Essential oils from A. conyzoides and L. multiflora were the most active on LNCaP and PC-3 cell lines, respectively. The SF-767 glioblastoma cell line was the most sensitive to O. basilicum and L. multiflora EOs while essential oil of A. conyzoides showed the highest activity on SF-763 cells. Altogether these results justify the use of these plants in traditional medicine in Burkina Faso and open a new field of investigation in the characterization of the molecules involved in anti-proliferative processes.