Background: The anticancer properties of Apocynaceae species are well known in barks and roots but less so in leaves. Materials and Methods: In this study, leaf extracts of 10 Apocynaceae species were assessed for antiproliferative (APF) activities using the sulforhodamine B assay. Their extracts were also analyzed for total alkaloid content (TAC), total phenolic content (TPC), and radical scavenging activity (RSA) using the Dragendorff precipitation, Folin-Ciocalteu, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays, respectively. Results: Leaf extracts of Alstonia angustiloba, Calotropis gigantea, Catharanthus roseus, Nerium oleander, Plumeria obtusa, and Vallaris glabra displayed positive APF activities. Extracts of Allamanda cathartica, Cerbera odollam, Dyera costulata, and Kopsia fruticosa did not show any APF activity. Dichloromethane (DCM) extract of C. gigantea, and DCM and DCM:MeOH extracts of V. glabra showed strong APF activities against all six human cancer cell lines. Against breast cancer cells of MCF-7 and MDA-MB-231, DCM extracts of C. gigantea and N. oleander were stronger than or comparable to standard drugs of xanthorrhizol, curcumin, and tamoxifen. All four extracts of N. oleander were effective against MCF-7 cells. Extracts of Kopsia fruticosa had the highest TAC while those of Dyera costulata had the highest TPC and RSA. Extracts of C. gigantea and V. glabra inhibited the growth of all six cancer cell lines while all extracts of N. oleander were effective against MCF-7 cells. Conclusion: Extracts of C. gigantea, V. glabra, and N. oleander therefore showed great promise as potential candidates for anticancer drugs. The wide-spectrum APF activities of these three species are reported for the first time and their bioactive compounds warrant further investigation.

Curcumin (CUR), a curcuminoid originating from turmeric root, possesses diverse pharmacological applications, including potent anticancer properties. However, the use of this efficacious agent in cancer therapy has been limited due to low water solubility and poor bioavailability. To overcome these problems, a drug delivery system was established as an excipient allowing improved dispersion in aqueous media coupled with enhanced in vitro anticancer effects. Different analyses such as UV–vis spectroscopy, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), solubility and dissolution assays were determined to monitor the successful encapsulation of CUR within the inner cavity of a β-cyclodextrin (β-CD) complex. The results indicated that water solubility was improved by 205.75-fold compared to pure CUR. Based on cytotoxicity data obtained from MTT assays, the inclusion complex exhibited a greater decrease in cancer cell viability compared to pure CUR. Moreover, cancer cell migration rates were decreased by 75.5% and 38.92%, invasion rates were decreased by 37.7% and 35.7%, while apoptosis rates were increased by 26.3% and 14.2%, and both caused caspase 3 activation toward colorectal cancer cells (SW480 and HCT116 cells). This efficacious formulation that enables improved aqueous dispersion is potentially useful and can be extended for various chemotherapeutic applications. Preliminary toxicity evaluation also indicated that its composition can be safely used in humans for cancer therapy.

Background: Studies have shown that the barks and roots of some Apocynaceae species have anticancer and antimalarial properties. In this study, leaf extracts of five selected species of Apocynaceae used in traditional medicine (Alstonia angustiloba, Calotropis gigantea, Dyera costulata, Kopsia fruticosa and Vallaris glabra) were assessed for antiproliferative (APF) and antiplasmodial (APM) activities, and analysed for total alkaloid content (TAC), total phenolic content (TPC) and radical-scavenging activity (RSA). As V. glabra leaf extracts showed wide spectrum APF and APM activities, they were further screened for saponins, tannins, cardenolides and terpenoids. Methods: APF and APM activities were assessed using the sulphorhodamine B and lactate dehydrogenase assays, respectively. TAC, TPC and RSA were analysed using Dragendorff precipitation, Folin-Ciocalteu and DPPH assays, respectively. Screening for saponins, tannins, cardenolides and terpenoids were conducted using the frothing, ferric chloride, Kedde and vanillin-H₂SO₄ tests, respectively. Results: Leaf extracts of A. angustiloba, C. gigantea and V. glabra displayed positive APF activity. Dichloromethane (DCM) extract of C. gigantea, and DCM and DCM:MeOH extracts of V. glabra showed strong APF activity against all six human cancer cell lines tested. DCM extract of A. angustiloba was effective against three cancer cell lines. Against MCF-7 and MDA-MB-231 cell lines, DCM extract of C. gigantea was stronger than standard drugs of xanthorrhizol, curcumin and tamoxifen. All five species were effective against K1 strain of Plasmodium falciparum and three species (C. gigantea, D. costulata and K. fruticosa) were effective against 3D7 strain. Against K1 strain, all four extracts of V. glabra displayed effective APM activity. Extracts of D. costulata were effective against 3D7 strain. Selectivity index values of extracts of A. angustiloba, C. gigantea and V. glabra suggested that they are potentially safe for use to treat malaria. Extracts of K. fruticosa had the highest TAC while D. costulata had the highest TPC and RSA. Phytochemical screening of extracts of V. glabra also showed the presence of terpenoids, tannins and saponins. Conclusions: Leaf extracts of C. gigantea and V. glabra showed great promise as potential candidates for anticancer drugs as they inhibited the growth of all six cancer cell lines. Against K1 strain of P. falciparum, all four extracts of V. glabra displayed effective APM activity. The wide spectrum APF and APM activities of V. glabra are reported for the first time and this warrants further investigation into its bioactive compounds.

Triple-negative breast cancer is the main type of breast carcinoma that causes mortality among women because of the limited treatment options and high recurrence. Chronic inflammation has been linked with the tumor microenvironment (TME) in breast cancer progression.Clinacanthus nutans(CN) has gained much attention because of its anticancer properties, but its mechanism remains unclear. We aimed to study the qualitative phytochemical content and elucidate the cytotoxicity effects of CN on human triple-negative breast cancer (TNBC), MDA-MB-231 and human macrophage-like cells such as THP-1 by using sulforhodamine B (SRB) assay. As highly metastatic cells, MDA-MB-231 cells can migrate to the distal position, the effect of CN on migration were also elucidated using the scratch assay. The CN effects on ameliorating chronic inflammation in TME were studied following the co-culture of MDA-MB-231/THP-1 macrophages. The cytokine expression levels of IL-6, IL-1β and tumor necrosis factor-alpha (TNF-α) were determined using ELISA assays. The results showed that both ethanolic and aqueous CN extracts contained alkaloid, phenol and tannin, flavonoid, terpenoid, glycoside and steroid. However, saponin was only found in the aqueous extract of CN. CN was not cytotoxic to both MDA-MB-231 and THP-1 cells. The ability of MDA-MB-231 to migrate was also not halted by CN treatment. However, CN ethanol extract decreased IL-6 at 25 μg/mL (p= 0.02) and 100 μg/mL (p= 0.03) but CN aqueous extract increased IL-6 expression at 50 μg/mL (p= 0.08) and 100 μg/mL (p= 0.02). IL-1β showed decreased expression after treated with CN ethanol and CN aqueous both at 25 μg/mL (p= 0.03). TNF-α were significantly decreased after CN ethanol treatment at concentration 25- (p = 0.001), 50- (p = 0.000) and 100 μg/mL (p= 0.000). CN aqueous extract slightly inhibited TNF-α at all 25–50- and 100 μg/mL (p = 0.001, p = 0.000, p = 0.000, respectively). Overall, CN acts by ameliorating the pro-inflammatory condition in the TME and may be a potential strategy for its anticancer mechanism on highly metastatic breast cancer condition. The major pathways that link both cancer and inflammation were NF-κB and STATs thus further study on the upstream and downstream pathways is needed to fully understand the mechanism of CN extracts in cooling the inflamed TME in breast cancer.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that is often associated with a poorer prognosis and does not respond to hormonal therapy. Increasing evidence highlights the exploitability of Annexin A1 (AnxA1), a calcium dependent protein, as a precision medicine for TNBC. To systematically summarize the role of AnxA1 and its associated mechanisms in TNBC, we performed data mining using three main databases: PubMed, Scopus, and Ovid/Medline. The papers retrieved were based on two different sets of key words such as “Annexin A1” or “Lipocortin 1” and “Breast cancer” or “TNBC”. A total of 388 articles were identified, with 210 chosen for comprehensive screening and 13 papers that met inclusion criteria were included. Current evidence from cell culture studies showed that AnxA1 expression is correlated with NF-κB, which promotes migration by activating ERK phosphorylation. AnxaA1 also activates TGF-β signaling which upregulates MMP-9 and miR196a expression to enhance epithelial-mesenchymal transition and migratory capacity of TNBC cells. AnxA1 can steer the macrophage polarization toward the M2 phenotype to create a pro-tumor immune environment. Existing research suggests a potential role of AnxA1 in the metastasis and immune landscape of TNBC tumors. Preclinical and clinical experiments are warranted to investigate the feasibility and effectiveness of targeting AnxA1 in TNBC.

Early diagnosis improves the prognosis for cancer patients by allowing early intervention to slow or prevent cancer development and lethality. Aptamers are short single-stranded oligonucleotides that have a length of about 2580 bases. They are produced chemically and extracted using the systematic evolution of ligands by exponential enrichment (SELEX). The use of aptamers as diagnostic tools in cancer is highly recommended due to their ability to recognize various cancer-related molecules and biomarkers with high affinity and specificity. Despite the clear advantages of aptamers, the potential of aptamers in cancer diagnosis is yet to be reached. This chapter will present the best available knowledge on using aptamers as the biorecognition element in the development of cancer biosensors. We will first present the advantages of aptamers in cancer diagnosis as well as various types of SELEX methods with emphasis on clinically relevant samples such as serum, whole cells, and tissue slices. We will also cover the various aptamer detection platforms, such as colorimetric, fluorescence, and electrochemical platforms. Furthermore, the updates on aptamers specific to KRAS mutation detection in cancer will be reviewed. Finally, the future direction of aptamers in cancer diagnosis will also be discussed.