Characterization of the anti-angiogenesis activity of labisia pumila and identification of its molecular constituents that contribute to its biological activity.

Angiogenesis is a process of new blood vessel formation. Inhibition of angiogenesis is considered one of the most promising strategies in treating variety of illnesses including cancer. Labisia Pumila var. alata (Myrsiaceae) or locally known as ‘kacip fatimah’, a lowland plant, is used widely by the Malays in Peninsular Malaysia to treat many health problems and ailments. Angiogenesis merupakan suatu proses pembentukan pembuluh darah baru. Penghalangan angiogenesis merupakan strategi yang penting dalam rawatan pelbagai penyakit termasuk kanser. Labisia pumila var alata (Myrsiaceae) atau lebih dikenali dengan nama tempatannya sebagai ‘kacip fatimah’ merupakan tumbuhan di tanah rendah lazimnya digunakan secara meluas oleh penduduk Melayu di Semenanjung Malaysia dalam rawatan pelbagai penyakit di negara ini

Anti-cancer effects of Vernonia amygdalina: A systematic review

Purpose: To systematically review all the studies that have addressed the anti-cancer activities of the VA leaf extract in vitro to determine the strength of evidence of its anti-cancer effects and whether it can be used as an effective cancer therapy.Methods: The databases of Scopus, Science Direct, PubMed, Springer, and Directory of Open Access Journals were searched for relevant articles. Only articles published in the English language from January 2000 to November 2018 were selected for full-text retrieval and review, before being included in the final review.Results: From a total of 28 articles identified for full-text retrieval, only 17 fulfilled the inclusion criteria. The papers reviewed showed that VA decreases cell viability, inhibits DNA synthesis and causes DNA damage in cancer cells. VA also induces apoptosis and cell cycle arrest in cancer cells via gene regulation. All in all, there is evidence showing that VA possesses time- and concentration-dependent anti-cancer activity.Conclusion: The VA leaf extract has the potential to be developed into cancer therapeutics. However, more research is needed on its effect on normal cells before VA is developed into a cancer therapeutic. Keywords: Vernonia amygdalina, Anti-cancer effect, DNA damage, Apoptosi

Inhibitory effect of Labisia pumila leaf extract on angiogenesis via down-regulation of vascular endothelial growth factor

Purpose: To investigate the anti-angiogenic activity of a methanol leaf extract of Labisia pumila (ME), and its bioactive water fraction (WF), using in vitro models.Methods: The antioxidant activity and total phenolic contents of ME and WF were assessed using DPPH and Folin–Ciocalteu reagents. Antiproliferative effects of extracts towards human umbilical vein endothelial cells (HUVECs) were evaluated using MTT assay. Isolated rat aortic ring and matrigel tube formation assays were performed to assess the antiangiogenic potential of Me and its WF. Levels of VEGF protein in the cell lysates were measured using ELISA kit.Results: Among all the extracts prepared, ME and its WF showed higher total phenolic contents and exhibited moderate antioxidant effects. Significant (p < 0.001) suppression of microvessels outgrowth with half-maximal concentration (IC50) values of 20 and 26 μg/mL for ME and WF, was observed in rat aortic ring assay. ME and its WF halted proliferation and tube formation capacity of HUVECs in in vitro assays. Marked reduction in VEGF levels was observed in lysates of HUVECs treated with ME and its WF.Conclusion: Labisia pumila leaf extract and its water fraction halted angiogenesis by blocking VEGF secretion leading to inhibition of endothelial cells proliferation and differentiation which is suggested to be due to its phenolic antioxidant contents.Keywords: Labisia pumila, Anti-angiogenesis, Antioxidant, Tube formation, Rat aort

Cytotoxicty of zerumbone against liver cancer cell lines (HepG2) via apoptosis activity

Zerumbone (ZER), a sesquiterpene phytochemical isolated from a type of edible ginger known as "Zingiber Zerumbet Smith" grown in Southeast Asia. The anticancer effects of ZER has been previously reported at our Laboratory, which used MTT assay on human cancer cells of several cell lines such as cervix (HeLa), leukemia (jurkat) and breast (MCF-7). ZER anti-cancer properties were found to be in equivalent with cisplatin, a commercial anticancer drug used preferentially in treating cervical cancer in humans. In this study, MTT assay was carried to obtain the IC50 value of zerumbone towards HepG2 and normal liver, WRL-68 cell lines. The cytotoxicity analysis on HepG2 cells revealed that the IC50 is 6.20μg/ml. ZER showed no apparent cytotoxicity response towards WRL-68 cell lines. Morphological analysis for apoptosis detection by using inverted microscope and SEM have produced typical apoptotic characteristic. It showed that zerumbone has antiproliferative activity towards liver cancer cell by its ability to induce apoptosis. The outcome of this study demonstrates that zerumbone has the ability to increased efficacy with limited toxicity in liver cancer treatment

In vivo assessment of nanostructured lipid carrier for oral delivery of zerumbone in leukemic mice model

Cancer nanotherapeutics are progressing rapidly with innovative drug delivery systems to replace conventional delivery systems. Although, antitumor activity of zerumbone (ZER) has been reported, there has been no available information of ZER-loaded nanostructured lipid carrier (NLC) affects murine leukemia cells in vivo. In a previous study, ZER was incorporated into NLC by high pressure homogenization (HPH) technique. Physicochemical characterization included particle size, polydipersity index, zeta potential, pH, entrapment efficiency, loading capacity, stability study, and in vitro drug release, as well as physicochemical stability after being autoclaved and stored at 4˚C, 25˚C and 40˚C for 1 month, were examined. In this study, in vivo effects of ZER-NLC on murine leukemia WEHI-3B cells were investigated. The outcomes of histopathology, TEM and TUNEL assays of BALB/c leukemia mice revealed that the number of leukemia cells were significantly (P < 0.05) decreased in spleen tissue after four weeks of oral administration of ZER-NLC. In conclusion, NLC is suggested as a promising carrier for ZER oral delivery

In vitro anti-angiogenic properties of ethanolic crude extract of Vernonia amygdalina

Angiogenesis is the process of generating new blood vessels that deliver tumor cells with oxygen and essential nutrients for growth and metastasis. This study examined the in vitro antiangiogenic properties of the ethanolic crude extract from Vernonia amygdalina (VA) grown in Malaysia. The direct antiangiogenic activity of VA was evaluated on EA.hy926 cells using in vitro assessments: Cell proliferation, colony formation, migration, and cell invasion assays. VA ethanolic crude extract cytotoxic activity was evident in the antiproliferative and colony formation assays. The growth inhibition (IC50) of 50% against EA.hy926 endothelial cells was achieved after 72 h treatment at a concentration of 85.43±3.57 μg/mL. Upon 48 h treatment, colony formation was inhibited completely at 100 μg/mL while 51.94% inhibition was achieved at 50 μg/mL. Moreover, the extract showed 54.72% and 31.99% inhibitory effects against migration of cells when treated for 24 h treatment at two different concentrations, 25 μg/mL and 12.5 μg/mL, respectively. The use of 100 μg/mL VA ethanolic extract inhibited cell invasion by 35.43%, which was lower than that of 57.81% inhibition achieved by the vinblastine as a positive control. All in all, the present work clearly demonstrated the antiangiogenic properties of VA ethanolic extract that may reflect a chemotherapeutic and/or chemoprevention potential for biomedical applications

Antiproliferative Efficacy of Zerumbone-Loaded Nanostructured Lipid Carrier in BALB/C Mice Model of Breast Cancer

Recently, we showed that the antiproliferative effect of ZER-NLC on Jurkat cells is through the apoptotic intrinsic pathway via activation of caspase-3 and -9, release of cytochrome c (cyt-c) from mitochondria into cytosol, and subsequent cleavage of polyADP-ribose polymerase (PARP). However, there has been no available information of ZER-NLC affects murine breast cancer cells in vivo. Thus, In this study, in vivo effects of ZER-NLC on murine breast cancer 4T1 cells were investigated. Outcomes of histopathology, immunohistochemistry and TUNEL assays of BALB/c mice bearing breast cancer revealed that the number of cancer cells were significantly decreased in mammary gland tissues after four weeks of oral administration of various doses of ZER-NLC

Isolation, purification and evaluation of anticancer principle from Zingiber zerumbet

The Zingiberaceae family is found in tropical and subtropical areas, with approximately 161 species from 18 genera of this family found in Peninsular Malaysia. Zingiber zerumbet (L.) Smith tree belonging to this family is an edible ginger, originating in South-East Asia, and has been cultivated for thousands of years as a spice and for medical purposes. The aim of this study is to isolate the active principle from extracted essential oil of fresh Zingiber Zerumbet rhizomes by steam-hydrodistillation method. In addition, to determine the purity of this active compound using validated reverse phase high performance liquid chromatography (RP-HPLC). Moreover, the antiproliferative effects of this active principal on various human cancerous and noncancerous cell lines at concentrations of 1 to 100 μg/mL were quantified by MTT assay. As a result, colorless zerumbone (ZER) crystals about 1.3 g/kg as an active principal were extracted from the essential oil of fresh Z. Zerumbet rhizomes. The purity of ZER crystals were shown to be (99.96%). Simultaneously, ZER exhibited significant (P < 0.05) inhibitory effects towards various human cancerous cell lines, while not affected noncancerous cell lines. In conclusion, ZER is suggested to be further developed into a safe therapeutic compound for the treatment of various human cancers

Inhibitory effects of nipa palm vinegar on the carbohydrate hydrolysing enzymes

Nipa palm vinegar has been traditionally used to manage blood glucose levels by diabetic patients in Southeast Asia. This study was designed to evaluate the efficacy of nipa palm vinegar in inhibiting the activity of carbohydrate hydrolyzing enzymes, α-glucosidase, and α-amylase. In vitro spectrophotometric assays were used to evaluate the inhibitory activity of nipa palm activity against α-glucosidase and α-amylase. To confirm the in vitro findings, an oral starch tolerance test in the normoglycemic Sprague Dawley rat was conducted. Acarbose was used as the positive control for both tests. Nipa palm vinegar at a concentration ranging from 4000 to 62.5 mg/mL inhibited the activity of α-glucosidase and α-amylase in a concentration-dependent manner with the respective IC50 values of 144.50 ± 1.1 mg/mL and 90.30 ± 1.7 mg/mL. It also exerted uncompetitive inhibition against α-glucosidase and competitive inhibition towards α-amylase. In vivo oral starch tolerance test showed a significant (p < 0.05) postprandial glucoselowering effect of nipa palm vinegar at the doses of 2 mL/kg and 1 mL/kg body weight as compared to the control. In a conclusion, this study demonstrated that nipa palm vinegar suppressed the rise in postprandial glucose levels partly by inhibiting the activity of digestive enzymes

Anti-angiogenic and anti-hepatocellular carcinoma properties of zerumbone extracted from Zingiber Zerumbet (l.) Smith

Zerumbone (ZER) extracted from Zingiber zerumbet is known to have anti-cancer properties; however, its mechanism in curbing liver cancer growth and spread is still not clear. Thus the objective of this study is determine the in vitro anti-cancer effect of ZER towards HepG2 cell line and the in vivo effect on induced rat hepatocellular carcinoma (HCC). The anti-cancer mechanisms investigated were apoptosis, antiproliferation and anti-angiogensis. Zerumbone was shown to be toxic towards HepG2 cells with IC50 of 6.20±0.70 µg/mL and less toxic towards normal liver cells (WRL68) with IC50 of 61.00±0.40µg/mL. The study showed that ZER caused cell cycle arrest at the G2/M phase and apoptosis, demonstrated by chromatin condensation, cell shrinkage and formation of apoptotic bodies in the HepG2 cells in a time-dependent manner. Zerumbone also stimulated caspase-3 and -9 activities in the HepG2 cells, suggesting that the induction of apoptosis was via the mitochondrial pathway. The study employed the diethylnitrosamine-induced rat HCC model and the rat aortic ring to determine the effect of ZER treatment. The study showed that ZER significantly (p<0.05) inhibited microvessel outgrowth in the aortic ring model. Zerumbone at 12.5 µg/mL caused the most significant (p<0.05) 98±1.28% blood vessels inhibition compared with the control and inhibited endothelial tube formation at 96.00±0.72%. This study showed that ZER treatment decreases expression of VEGF, MMP-9 and Ki- 67 in the rat HCC tissue as well as and inhibits neovascularization in the chick embryo. The treatment had also induced apoptosis in HCC. The ZER-treated liver tissues with HCC showed normal hepatocyte orientation, unlike the untreated livers, which showed pleomorphic hepatocytes and anaplastic appearance typical of HCC. It can be concluded from the study that the anti-cancer effect of ZER on the HepG2 cell line and HCC is multifaceted involving induction of cell cycle arrest, apoptosis, and suppression of VEGFR, VEGF, MMP-9 and Ki-67 proteins, leading to inhibition of angiogenesis. Since ZER was less toxic to the normal liver cells, this compound is a potentially effective anti-HCC agent, without significant side-effects and can be developed as a therapeutic regime either alone or in combination with other chemotherapeutic agents