Pathways Related to the Anti-Cancer Effects of Metabolites Derived from Cerrado Biome Native Plants: An Update and Bioinformatics Analysis on Oral Squamous Cell Carcinoma.

BACKGROUND: Oral cancer is a significant health problem worldwide. Oral squamous cell carcinoma (OSCC) is a malignant neoplasm of epithelial cells that mostly affects different anatomical sites in the head and neck and derives from the squamous epithelium or displays similar morphological characteristics. Generally, OSCC is often the end stage of several changes in the stratified squamous epithelium, which begin as epithelial dysplasia and progress by breaking the basement membrane and invading adjacent tissues. Several plant-based drugs with potent anti-cancer effects are considered inexpensive treatments with limited side effects for cancer and other diseases. OBJECTIVE: The aim of this review is to explore whether some Brazilian plant extracts or constituents exhibit anti-tumorigenic activity or have a cytotoxic effect on human oral carcinoma cells. METHODS: Briefly, OSCC and several metabolites derived from Brazilian plants (i.e., flavonoids, vinblastine, irinotecan, etoposide and paclitaxel) were used as keywords to search the literature on PubMed, GenBank and GeneCards. RESULTS: The results showed that these five chemical compounds found in Cerrado Biome plants exhibit anti-neoplastic effects. Evaluating the compounds revealed that they play a main role in the regulation of cell proliferation. CONCLUSION: Preserving and utilising the biodiversity of our planet, especially in unique ecosystems, such as the Cerrado Biome, may prove essential to preserving and promoting human health in modern contexts.

Biotechnological advancements in Catharanthus roseus (L.) G. Don.

Catharanthus roseus (L.) G. Don, also known as Madagascar periwinkle or Sadabahar, is a herbaceous plant belonging to the family Apocynaceae. Being a reservoir for more than 200 alkaloids, it reserves a place for itself in the list of important medicinal plants. Secondary metabolites are present in its leaves (e.g., vindoline, vinblastine, catharanthine, and vincristine) as well as basal stem and roots (e.g., ajmalicine, reserpine, serpentine, horhammericine, tabersonine, leurosine, catharanthine, lochnerine, and vindoline). Two of its alkaloids, vincristine and vinblastine (possessing anticancerous properties), are being used copiously in pharmaceutical industries. Till date, arrays of reports are available on in vitro biotechnological improvements of C. roseus. The present review article concentrates chiefly on various biotechnological advancements based on plant tissue culture techniques of the last three decades, for instance, regeneration via direct and indirect organogenesis, somatic embryogenesis, secondary metabolite production, synthetic seed production, clonal fidelity assessment, polyploidization, genetic transformation, and nanotechnology. It also portrays the importance of various factors influencing the success of in vitro biotechnological interventions in Catharanthus and further addresses several shortcomings that can be further explored to create a platform for upcoming innovative approaches. KEY POINTS: • C. roseus yields anticancerous vincristine and vinblastine used in pharma industry. •In vitro biotechnological interventions prompted major genetic advancements. • This review provides an insight on in vitro-based research achievements till date. • Key bottlenecks and prospective research methodologies have been identified herein.

Synthesis of Bisindole Alkaloids from the Apocynaceae Which Contain a Macroline or Sarpagine Unit: A Review.

Bisindole natural products consist of two monomeric indole alkaloid units as their obligate constituents. Bisindoles are more potent with respect to their biological activity than their corresponding monomeric units. In addition, the synthesis of bisindoles are far more challenging than the synthesis of monomeric indole alkaloids. Herein is reviewed the enantiospecific total and partial synthesis of bisindole alkaloids isolated primarily from the Alstonia genus of the Apocynaceae family. The monomeric units belong to the sarpagine, ajmaline, macroline, vobasine, and pleiocarpamine series. An up-to-date discussion of their isolation, characterization, biological activity as well as approaches to their partial and total synthesis by means of both synthetic and biosynthetic strategies are presented.

Negative-pressure cavitation extraction of four main vinca alkaloids from Catharanthus roseus leaves.

In the present study, an improved method termed negative-pressure cavitation extraction (NPCE) followed by reverse phase high-performance liquid chromatography (RP-HPLC) was developed for the extraction and quantification of vindoline (VDL), catharanthine (CTR), vincristine (VCR) and vinblastine (VLB) from Catharanthus roseus leaves. The optimized method employed 60-mesh particles, 80% ethanol, a negative pressure of -0.075 MPa, a solid to liquid ratio of 1:20, 30 min of extraction and three extraction cycles. Under these optimized conditions, the extraction yields of VDL, CTR, VCR and VLB are 0.5783, 0.2843, 0.018 and 0.126 mg/g DW, respectively. These extraction yields are equivalent to those from the well-known ultrasonic extraction method and higher than the yields from maceration extraction and heating reflux extraction. Our results suggest that NPCE-RP-HPLC represents an excellent alternative for the extraction and quantification of vinca alkaloids for pilot- and industrial-scale applications.

[Monomeric indole alkaloids from the aerial parts of Catharanthus roseus].

Catharanthus roseus (L.) G. Don is a plant of the Catharanthus genus of Apocynaceae which has been reported to have therapeutic effects of detoxication and anticancer. In order to further study the alkaloid constituents of C. roseus, the aerial parts of the plant were extracted with 95% EtOH, and then treated with 2% H2SO4 and NH3H2O to obtain total alkaloids. The total alkaloids were separated and purified by column chromatography over silica gel and prepared by high performance liquid chromatography (HPLC). Their structures were elucidated on the basis of physicochemical properties and spectral data. A new alkaloid together with five known compounds were isolated and identified as vindolinine B (1), lochnericine (2), horhammericine (3), vindorosine (4), vindoline (5), and coronaridine (6). Compound 1 is a new compound and named as vindolinine B.

Isolation and characterization of antineoplastic alkaloids from Catharanthus roseus L. Don. cultivated in Egypt.

Vinblastine and vincristine (the antileukemic agents) were isolated, in a pure form, from Catharanthus roseus L. Don., cultivated in Egypt, by several chromatographic techniques. Five modified methods for the preparation of total alkaloids were carried out. All the isolated mixtures were evaluated by HPLC and HPTLC analyses. The antineoplastic alkaloids; vinblastine and vincristine, were isolated by the use of vacuum liquid chromatographic column on silica gel : aluminium oxide (1:1) mixed bed vacuum liquid chromatography (VLC), Charcoal column, and finally purified by centrifugally accelerated radial chromatography (Chromatotrone).

In vitro cytotoxic activity of Salsola oppositifolia Desf. (Amaranthaceae) in a panel of tumour cell lines.

The aim of the present study was to evaluate for the first time the in vitro cytotoxic activity of fractions and isolated flavonols from Salsola oppositifolia Desf. (Amaranthaceae). The n-hexane fraction demonstrated an effective cytotoxic activity on the large lung carcinoma and amelanotic melanoma cell lines with IC50 values of 19.1 microg/ml and 24.4 microg/ml, respectively. Also the dichloromethane fraction exhibited cytotoxic activity against COR-L23 (IC50 30.4 microg/ml) and C32 (IC50 33.2 microg/ml) cells, while the EtOAc fraction demonstrated a selective cytotoxic activity against MCF-7 cells (IC50 67.9 microg/ml). The major active constituents of this fraction were isorhamnetin-3-O-glucoside (1) and isorhamnetin-3-O-rutinoside (2), which showed an interesting activity against the cell line MCF-7 with IC50 values of 18.2 and 25.2 microg/ml, respectively. Compound 2 exhibited a strong activity against the hormone-dependent prostate carcinoma LNCaP cell line with an IC50 of 20.5 microg/ml. Constituents of S. oppositifolia were identified by GC-MS and NMR analyses.

[Removal of the template molecules from vinblastine-imprinted polymer].

OBJECTIVE: To investigate the optimal condition for complete removal of the template molecules from vinblastine (VLB)-imprinted polymer. METHOD: The prepared polymers were packed into the cartridges of solid-phase extraction column and washed by methanol-glacial acetic acid mixture with different proportions. The contents and recoveries of VLB in the effluents were determined. RESULTS: Polymer extraction with methanol-glacial acetic acid (9:1, V/V) resulted in VLB recovery of 91.73%, but template bleeding was observed because of incomplete VLB removal. Using methanol-glacial acetic acid (6:4, V/V) as the extraction solvent, the recovery of VLB reached 98.03% with less solvents and extract times. The polymers could selectively adsorb VLB through non-covalent interactions and still exhibited strong affinity for the template molecule but not for the structural analogue vincristine after extraction with methanol-glacial acetic acid (6:4, V/V). CONCLUSION: Methanol-glacial acetic acid (6:4, V/V) is an ideal extract solvent for complete template molecule removal from the polymers, and the processed polymers possess stable capacity of specific recognition and selectivity to the template.

[Optimization of the polymerization conditions of vinblastine imprinted polymer by uniform design].

OBJECTIVE: To optimize the polymerization conditions of vinblastine (VLB) imprinted polymer. METHODS: The conditions were optimized by the method of uniform design. The major factors investigated included the amount of functional monomer (MAA) and the cross-linker (EDMA) and the progenic solvent (toluene or acetonitril). The adsorption rate of VLB on the solid-phase extraction (SPE) column packed with MIP was adopted as the response value. RESULTS: The optimal conditions were MAA 0.4 mmol, EDMA 1.6 mmol and using acetonitrile as the solvent. Under the conditions,the VLB imprinted polymer was synthesized and the absorption rate of VLB was 88.20%. The characterizations of the optimal MIP were determined by IR spectrometry and scanning electron microscope (SEM) analysis. CONCLUSION: It is possible to furtherly improve the nature of the polymer by optimizing the polymerization parameters with uniform design. The polymer synthesized under the optimal conditions exhibited high affinity to the target molecule VLB.

Isolation of vindoline from Catharanthus roseus by supercritical fluid extraction.

Vindoline was extracted from the leaves of Catharanthus roseus over the ranges of 35-70 degrees C and 100-300 bar using supercritical carbon dioxide with and without the addition of 3 wt % ethanol as a cosolvent. The vindoline contents in the extracts were determined by HPLC and identified by LC/MS. The remarkable highest vindoline concentration, 58 wt %, was obtained at the lowest temperature, 35 degrees C, and the highest pressure, 300 bar, of this study. The use of a cosolvent only slightly improved the extraction yields or selectivities at some experimental conditions.

Isolation of Catharanthus alkaloids by solid-phase extraction and semipreparative HPLC.

A combination of moderate-pressure chromatography on C18 sorbent and preparative HPLC is developed for rapid isolation of alkaloids from Catharanthus roseus. The procedure is optimized for vindoline and catharanthine with respective yields of 3 and 2 mg per 1 g of dried leaves of the plant. The methodology is also applied for identification of the above and other alkaloids from cultured plant cells.

Modification of Catharanthus roseus alkaloids: a lactone derived from 17-deacetylvinblastine.

A spirolactone with anti-tumor activity is formed during the reaction of paraformaldehyde with 17-deacetylvinblastine. The compound was identified by NMR techniques. The chemotherapeutic activity was assessed.