Crude extract and solvent fractions of Calystegia soldanella induce G1 and S phase arrest of the cell cycle in HepG2 cells

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Abstract

The representative halophyte Calystegia soldanella (L) Roem. et Schult is a perennial vine herb that grows in coastal dunes throughout South Korea as well as in other regions around the world. This plant has long been used as an edible and medicinal herb to cure rheumatic arthritis, sore throat, dropsy, and scurvy. Some studies have also shown that this plant species exhibits various biological activities. However, there are few studies on cytotoxicity induced by C. soldanella treatment in HepG2 human hepatocellular carcinoma cells. In this study, we investigated the viability of HepG2 cells following treatment with crude extracts and four solvent-partitioned fractions of C. soldanella. Of the crude extract and four solvent fractions tested, treatment with the 85% aqueous methanol (aq. MeOH) fraction resulted in the greatest inhibition of HepG2 cell proliferation. Flow cytometry showed that the 85% aq. MeOH fraction induced a G0/G1 and S phase arrest of the cell cycle progression. The 85% aq. MeOH fraction arrested HepG2 cells at the G0/G1 phase in a concentration-dependent manner, and resulted in decreased expression of cyclin D1, cyclin E, cyclin-dependent kinase (CDK)2, CDK4, CDK6, p21, and p27. Additionally, the 85% aq. MeOH fraction treatment also arrested HepG2 cells in the S phase, with decreased expression of cyclin A, CDK2, and CDC25A. Also, treatment with this fraction reduced the expression of retinoblastoma (RB) protein and the transcription factor E2F. These results suggest that the 85% aq. MeOH fraction exhibits potential anticancer activity in HepG2 cells by inducing G0/G1 and S phase arrest of the cell cycle.

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Photosynthetic carbon assimilation and associated metabolism in relation to water deficits in higher plants.

D. W. LAWLOR, G. Cornic (2002)

Experimental studies on CO2 assimilation of mesophytic C3 plants in relation to relative water content (RWC) are discussed. Decreasing RWC slows the actual rate of photosynthetic CO2 assimilation (A) and decreases the potential rate (Apot). Generally, as RWC falls from c. 100 to c. 75%, the stomatal conductance (gs) decreases, and with it A. However, there are two general types of relation of Apot to RWC, which are called Type 1 and Type 2. Type 1 has two main phases. As RWC decreases from 100 to c. 75%, Apot is unaffected, but decreasing stomatal conductance (gs) results in smaller A, and lower CO2 concentration inside the leaf (Ci) and in the chloroplast (Cc), the latter falling possibly to the compensation point. Down-regulation of electron transport occurs by energy quenching mechanisms, and changes in carbohydrate and nitrogen metabolism are considered acclimatory, caused by low Ci and reversible by elevated CO2. Below 75% RWC, there is metabolic inhibition of Apot, inhibition of A then being partly (but progressively less) reversible by elevated CO2; gs regulates A progressively less, and Ci and CO2 compensation point, Gamma rise. It is suggested that this is the true stress phase, where the decrease in Apot is caused by decreased ATP synthesis and a consequent decreased synthesis of RuBP. In the Type 2 response, Apot decreases progressively at RWC 100 to 75%, with A being progressively less restored to the unstressed value by elevated CO2. Decreased gs leads to a lower Ci and Cc but they probably do not reach compensation point: gs becomes progressively less important and metabolic limitations more important as RWC falls. The primary effect of low RWC on Apot is most probably caused by limited RuBP synthesis, as a result of decreased ATP synthesis, either through inhibition of Coupling Factor activity or amount due to increased ion concentration. Carbohydrate synthesis and accumulation decrease. Type 2 response is considered equivalent to Type 1 at RWC below c. 75%, with Apot inhibited by limited ATP and RuBP synthesis, respiratory metabolism dominates and Ci and Gamma rise. The importance of inhibited ATP synthesis as a primary cause of decreasing Apot is discussed. Factors determining the Type 1 and Type 2 responses are unknown. Electron transport is maintained (but down-regulated) in Types 1 and 2 over a wide range of RWC, and a large reduced/oxidized adenylate ratio results. Metabolic imbalance results in amino acid accumulation and decreased and altered protein synthesis. These conditions profoundly affect cell functions and ultimately cause cell death. Type 1 and 2 responses may reflect differences in gs and in sensitivity of metabolism to decreasing RWC.

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Targeting the extrinsic apoptosis pathway in cancer.

Avi Ashkenazi (2015)

Mutational inactivation of the p53 tumor-suppressor gene, which regulates apoptosis mainly via the cell-intrinsic pathway, reduces the sensitivity of many cancers to conventional treatments. Targeting the cell-extrinsic pathway, which triggers p53-independent apoptosis, offers a unique therapeutic strategy to induce apoptosis in cancer cells. This article focuses on two proapoptotic receptor agonists, recombinant human Apo2-ligand/TNF-related apoptosis-inducing ligand (rhApo2L/TRAIL) and Apomab, which activate death receptor (DR) 4 and/or DR5, thus stimulating the cell-extrinsic pathway. These agents are under investigation for the treatment of solid tumor and hematologic malignancies. Preclinical data indicate that both molecules cause significant regression or growth inhibition of malignant tumors without significant toxicity. Initial data on rhApo2L/TRAIL and Apomab from phase 1 safety trials also confirm that these agents are suitable for further clinical investigation.

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Bioactive Compounds Isolated from Microalgae in Chronic Inflammation and Cancer

Elena Talero, Sofia Garcia-Maurino, Javier Ávila-Román … (2015)

The risk of onset of cancer is influenced by poorly controlled chronic inflammatory processes. Inflammatory diseases related to cancer development include inflammatory bowel disease, which can lead to colon cancer, or actinic keratosis, associated with chronic exposure to ultraviolet light, which can progress to squamous cell carcinoma. Chronic inflammatory states expose these patients to a number of signals with tumorigenic effects, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) activation, pro-inflammatory cytokines and prostaglandins release and ROS production. In addition, the participation of inflammasomes, autophagy and sirtuins has been demonstrated in pathological processes such as inflammation and cancer. Chemoprevention consists in the use of drugs, vitamins, or nutritional supplements to reduce the risk of developing or having a recurrence of cancer. Numerous in vitro and animal studies have established the potential colon and skin cancer chemopreventive properties of substances from marine environment, including microalgae species and their products (carotenoids, fatty acids, glycolipids, polysaccharides and proteins). This review summarizes the main mechanisms of actions of these compounds in the chemoprevention of these cancers. These actions include suppression of cell proliferation, induction of apoptosis, stimulation of antimetastatic and antiangiogenic responses and increased antioxidant and anti-inflammatory activity.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Oncol

Journal ID (iso-abbrev): Int. J. Oncol

Journal ID (publisher-id): IJO

Title: International Journal of Oncology

Publisher: D.A. Spandidos

ISSN (Print): 1019-6439

ISSN (Electronic): 1791-2423

Publication date Collection: February 2017

Publication date (Electronic): 02 January 2017

Publication date PMC-release: 02 January 2017

Volume: 50

Issue: 2

Pages: 414-420

Affiliations

[1 ]Institute of Fisheries Science, Pukyong National University, Ilgwang-myeon, Gijang-gun, Busan 619-911

[2 ]Department of Food Science and Nutrition, Pukyong National University, Nam-gu, Busan 48513, Republic of Korea

Author notes

Correspondence to: Professor Taek-Jeong Nam, Department of Food Science and Nutrition, Pukyong National University, 45 Yongso-ro, Nam-gu, Busan 48513, Republic of Korea, E-mail: namtj@ 123456pknu.ac.kr

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Publisher ID: ijo-50-02-0414

DOI: 10.3892/ijo.2017.3836

PMC ID: 5238786

PubMed ID: 28101580

SO-VID: 33a9b7f5-3768-48c8-8393-c2d0a88e38ae

License:

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Crude extract and solvent fractions of Calystegia soldanella induce G1 and S phase arrest of the cell cycle in HepG2 cells

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Most cited references 53

Photosynthetic carbon assimilation and associated metabolism in relation to water deficits in higher plants.

Targeting the extrinsic apoptosis pathway in cancer.

Bioactive Compounds Isolated from Microalgae in Chronic Inflammation and Cancer

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