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Background: Clinacanthus nutans possesses several reported biological activities against different human cancer cells. However, reports on the growth-inhibitory effect of C. nutans leaf extract on the aggressive triple-negative breast cancer cells and the mechanisms of induced-cell death in these cells are limited. Objectives: The study aimed to assess the anticancer efficacy and associated mechanisms of the crude aqueous extract of C. nutans leaves (cCN) in MDA-MB-231 triple-negative human breast cancer cells. Materials and Methods: The metabolic viability of the MDA-MB-231 cells following respective treatments with cCN was measured using an adenosine triphosphate luminescent assay. The mode of cell death in MDA-MB-231 cells induced by cCN was examined using a luminescence- and fluorescence-based assay and the mechanisms involved were evaluated by comparative analysis of gene expression by reverse transcription–quantitative polymerase chain reaction. Results: Dose- and time-dependent growth inhibition of MDA-MB-231 cells by cCN was observed (IC50: 191.20 μg/mL). cCN also induced apoptotic cell death in the treated cells via the intrinsic and extrinsic apoptosis pathways by affecting the mRNA expression levels of Bad, Bax, Bcl-2, Bcl-xL, and FasL. Conclusion: These results suggest that C. nutans can be used as a potential agent in the treatment and prevention of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Clinacanthus nutans (CN) is a small shrub native to tropical Asia known for their anti-oxidant, anti-inflammation, anti-cancer, and anti-viral activities. Objectives: This study aimed to investigate the effect of CN extract on human embryonic kidney cell line (HEK-Blue™-4) in a proteomic perspective. Materials and Methods: Comparative proteomic profiling through two-dimensional sodium dodecyl sulfate gel electrophoresis was performed on HEK-Blue™-4 treated with CN leaf polar extract. Results: We successfully identified seven upregulated proteins, of which five promoted the growth of the HEK-Blue™-4 cells. Interestingly, a potent antioxidant enzyme which neutralizes reactive oxygen or nitrogen species, peroxiredoxin-1 was also upregulated in HEK-Blue™-4 cell lines after treatment with CN leaf polar extract. Conclusion: CN leaf polar extract promotes the growth of HEK-Blue™-4 cells and induced the expression of peroxiredoxin-1, which protects the cells from reactive oxygen species during the inflammation process. [ABSTRACT FROM AUTHOR]

Introduction: Clinacanthus nutans (Burm. f.) Lindau, a shrub found in South East Asia, particularly in Malaysia, Thailand, and Indonesia has many potential medicinal uses. It is used as a traditional herbal medicine for treating many diseases including skin rashes. Skin rash often appear in an allergic reaction. Recently, we have shown that C. nutans aqueous extract has the ability to alleviate ovalbumin-induced active systemic anaphylaxis rats from anaphylaxis – the acute form of allergy. This present study is aimed at comparing the ability of ethanolic and aqueous extracts of C. nutans to suppress IgE-mast cell degranulation. Materials and Methods: IgE-presensitized rat basophilic leukemic (RBL-2H3) cells pretreated with C. nutans ethanolic (100% ethanolic, 70% and 50% aqueous ethanolic) or 100% aqueous extracts were challenged with dinitrophenyl-bovine serum albumin to analyze the release of early and late-phase pro-inflammatory mediators. Results: We found that at concentrations of 5 mg/ml and above, C. nutans aqueous extract was able to suppress the levels of β-hexosaminidase and histamine while suppression was not seen in ethanolic extracts pretreated RBL-2H3 cells.Conclusion: Hence, we proposed that C. nutans aqueous extract is more active compared to the ethanolic extracts in suppressing the mediators of IgE-mast cell degranulation. [ABSTRACT FROM AUTHOR]

Introduction: The methanolic extracts of Clinacanthus nutans (CME) and Strobilanthes crispus (SME) are used in Malaysia as a complementary and alternative medicine for cancer. Objective: The present study aimed to determine the antioxidative and photocytotoxic effects of CME and SME toward liver cancer cells. Materials and Methods: Cell-based (2′,7′-dichlorodihydrofluorescein diacetate) and chemical-based (2,2-diphenyl-1-picrylhydrazyl [DPPH]) experiments were utilized to determine the antioxidative properties of both herbal extracts. CME and SME were also tested for their photocytotoxic potentials after photodynamic therapy (PDT). Phytochemical analysis was performed to identify the phytocompounds present in the extracts. Results: Both the extracts demonstrated dose-dependent DPPH radical scavenging activities, while SME was found to be a stronger reactive oxygen species scavenger than CME at all concentrations tested on liver cells. Interestingly, on PDT, HepG2 cells treated with SME and CME at non-toxic doses showed a decrease in cellular viability charting half-maximal inhibitory concentration of 13.45 μg/mL and 81.03 μg/mL, respectively. Total phenolic content of SME (36.27 ± 1.31 mg GAE/g extract) was slightly higher than CME (31.76 ± 0.10 mg GAE/g extract). On the contrary, the total flavonoid content of CME (11.32 ± 0.28 mg QE/g extract) was approximately seven times more than SME (1.69 ± 0.03 mg QE/g extract). Phenolic acids, flavonoids, and pheophorbide-a were identified in both extracts. In view of this, these phytocompounds present in CME and SME could lead to the observed beneficial effects. Conclusion: CME and SME, especially the latter, are strong antioxidants with photosensitizing potentials that should be further investigated. [ABSTRACT FROM AUTHOR]

Background: Clinacanthus nutans (Burm.f.) Lindau is a medicinal herb that is conventionally used for the treatment of skin rashes, insect bites, snake bites, diabetes, and cancer. Objective: Our study aims to investigate the apoptosis- and autophagy-inducing effects of C. nutans in HCT116 human colorectal cancer cells. Materials and Methods: Cytotoxicity of ethanol extract, hexane, ethyl acetate, and aqueous fractions of C. nutans against various cancer cell lines was determined via MTT assay. Apoptosis assays including annexin V, mito-ID, and Hoechst 33342/propidium iodide staining were carried out. The level of intracellular reactive oxidative species was determined using flow cytometry. Western blot analysis was carried out to assess the protein expression in C. nutans ethyl acetate fraction (CNEAF)-treated HCT116 cells. Results: CNEAF was found to exert the strongest cytotoxic effect against HCT116 cells (IC50 =48.81 ± 1.44 μg/mL). CNEAF-induced apoptosis was evidenced by nuclear morphological alterations, phosphatidylserine externalization, dissipation of mitochondrial membrane potential, and elevation of intracellular reactive oxygen species (ROS) level. Dissipation of mitochondrial membrane potential was attributed to the upregulation of Bax and Bak accompanied by downregulation of Bcl-2 and Bcl-xL, leading to caspase-3, -9, -8, and -10 activation. Interestingly, an upregulation of death receptor 5 was detected, suggesting involvement of intrinsic and extrinsic pathways. In addition, the occurrence of autophagy by CNEAF was supported by LC-3 accumulation and p62 degradation. The reduction of intracellular ROS level by N-acetylcysteine showed that the apoptosis and autophagy induced by CNEAF is ROS dependent. Conclusions: CNEAF induced ROS-dependent apoptosis and autophagy on HCT116 cells. Abbreviations used: CNEAF: Clinacanthus nutans ethyl acetate fraction; ROS: Reactive oxygen species; PS: Phosphatidylserine; NAC:N-Acetyl Cysteine; Bax: Bcl-2-associated X; Bcl-2: B-cell lymphoma 2; DR-5: Death receptor 5 Bak: Bcl-2-antagonist/killer 1; Bcl-xL: B-cell lymphoma-extra large. [ABSTRACT FROM AUTHOR]