In vitro cytotoxic potential of Polyalthia longifolia on human cancer cell lines and induction of apoptosis through mitochondrial-dependent pathway in HL-60 cells. Chem Biol Interact, 171, 45-56

Department of Pharmacology, Indian Institute of Integrative Medicine, Jammu, India.
Chemico-Biological Interactions (Impact Factor: 2.58). 02/2008; 171(1):45-56. DOI: 10.1016/j.cbi.2007.08.010
Source: PubMed


Polyalthia longifolia is a lofty evergreen tree found in India and Sri Lanka. We are reporting first time the anticancer potential of P. longifolia leaves extract (A001) and its chloroform fraction (F002). Both inhibited cell proliferation of various human cancer cell lines in which colon cancer cells SW-620 showed maximum inhibition with IC(50) value 6.1 microg/ml. Furthermore, F002 induce apoptosis in human leukemia HL-60 cells as measured by several biological end points. F002 induce apoptotic bodies formation, DNA ladder, enhanced annexin-V-FITC binding of the cells, increased sub-G(0) DNA fraction, loss of mitochondrial membrane potential (DeltaPsi(mt)), release of cytochrome c, activation of caspase-9, caspase-3, and cleavage of poly ADP ribose polymerase (PARP) in HL-60 cells. All the above parameters revealed that F002-induced apoptosis through the mitochondrial-dependent pathway in HL-60 cells.

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Available from: Monika Verma, May 27, 2015
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    • "The apoptotic rates were measured by Annexin V-PE and 7-ADD staining after 12,24 h following various treatments. The fractions of cells in each quadrant were analyzed by quadrant statistics [16]. As shown in Figure 7, the percentages of cells with Annexin V-positive staining increased gradually in a concentration-dependent manner after Gyp treatment, suggesting that Gyp could induce apoptotic response in SW-480 cells. "
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    ABSTRACT: Gypenosides (Gyp), the main components from Gynostemma pentaphyllum Makino, are widely used in traditional Chinese medicine. The present study aimed to investigate the anti-cancer effect and the underlying mechanisms of Gyp on human colorectal cancer cells SW-480. The inhibitory effect of Gyp on SW-480 cells was evaluated by MTT assay. Apoptotic cell death was detected by nuclear Hoechst 33342 staining and DNA fragmentation analysis. Apoptosis was analyzed using Annexin V-PE/7-amino-actinomycin D staining. Cell membrane integrity was evaluated with flow cytometry following PI staining. Changes of mitochondrial membrane potential (Δψm) were detected through flow cytometry analysis of rhodamine 123 (Rh123). The role of reactive oxygen species (ROS) in Gyp induced cell death was investigated by intracellular ROS generation and general ROS scavenger. Wound-healing assay was carried out to investigate Gyp-inhibited migration of SW-480 cells in vitro. Additionally, the alterations in F-actin microfilaments were analyzed by FITC-labeled phalloidin toxin staining and the morphological changes were evaluated under scanning electron microscope (SEM). After the Gyp treatment, the plasma membrane permeability of SW-480 cell was increased, Δψm was decreased significantly, the level of intracellular ROS level was increased, DNA fragmentation and apoptotic morphology were observed. Cells treated with Gyp exert serious microfilament network collapse as well as the significant decrease in the number of microvilli. Gyp induced the changes of cell viability, cell migration, intracellular ROS generation and nuclear morphology were alleviated obviously by NAC. The results in this study implied that ROS play an important role in Gyp induced cell toxicity and apoptosis, and the mitochondria damage may be upstream of ROS generation post Gyp treatment. The findings of the present study provide new evidences for anti-tumor mechanisms by which Gyp induces apoptosis in vitro.
    PLoS ONE 04/2014; 9(4):e95609. DOI:10.1371/journal.pone.0095609 · 3.23 Impact Factor
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    • "About 60% of the anticancer drugs are derived from plant sources, for example, taxol from Taxus brevifolia and camptothecin from Cuscuta reflexa [39]. Anticancer drug having low side effects, inducing apoptosis and targeting specific cytotoxicity to the cancer cells, is the drug of choice [2, 25]. "
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    ABSTRACT: The present work reports the anticancer, antioxidant, lipo-protective, and anti-HIV activities of phytoconstituents present in P. hysterophorus leaf. Dried leaf samples were sequentially extracted with nonpolar and polar solvents. Ethanol fraction showed noticeable cytotoxic activity (81-85%) in SRB assay against MCF-7 and THP-1 cancer cell lines at 100 μ g/ml concentration, while lower activity was observed with DU-145 cell line. The same extract exhibited 17-98% growth inhibition of HL-60 cancer cell lines in MTT assay, showing concentration dependent response. Ethanol extract caused 12% reduction in mitochondrial membrane potential and 10% increment in sub G1 population of HL-60 cell lines. Several leaf fractions, namely, ethyl acetate, ethanol, and aqueous fractions exhibited considerable reducing capability at higher concentrations. Most of the extracts demonstrated appreciable (>75%) metal ion chelating and hydroxyl radical scavenging activities at 200 µg/ml. All the extracts except aqueous fraction accounted for about 70-80% inhibition of lipid peroxidation in rat liver homogenate indicating protective response against membrane damage. About 40% inhibition of reverse transcriptase (RT) activity was observed in hexane fraction in anti-HIV assay at 6.0 µg/ml concentration. The study showed that phytochemicals present in P. hysterophorus leaf have considerable potential as cytotoxic and antioxidant agents with low to moderate anti-HIV activity.
    11/2013; 2013(3):810734. DOI:10.1155/2013/810734
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    • "Over 6 million people die due to cancer each year worldwide, indicating it to be the largest single cause of death in both men and women [13]. About 60% of the anticancer drugs are derived from plant sources, for example, taxol from Taxus brevifolia and camptothecin from Cuscuta reflexa [14]. Anticancer drug having low side effects, inducing apoptosis and target specific cytotoxicity to the cancer cells, are drug of choice [15]. "
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    09/2013; 2013(6):915436. DOI:10.1155/2013/915436
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