alexa Hypothesis: Spirulina may Slow the Growth and Spread of Ovarian Cancer by Interfering with Growth Factor Activity of Lysophophatidic Acid | Open Access Journals
ISSN: 1747-0862
Journal of Molecular and Genetic Medicine
Make the best use of Scientific Research and information from our 700+ peer reviewed, Open Access Journals that operates with the help of 50,000+ Editorial Board Members and esteemed reviewers and 1000+ Scientific associations in Medical, Clinical, Pharmaceutical, Engineering, Technology and Management Fields.
Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 600+ Conferences, 1200+ Symposiums and 1200+ Workshops on
Medical, Pharma, Engineering, Science, Technology and Business

Hypothesis: Spirulina may Slow the Growth and Spread of Ovarian Cancer by Interfering with Growth Factor Activity of Lysophophatidic Acid

Mark F McCarty*

Catalytic Longevity, 7831 Rush Rose Dr., Apt. 316, Carlsbad, USA

Corresponding Author:
Mark F McCarty, B.A.
Catalytic Longevity, 7831 Rush Rose Dr., Apt. 316
Carlsbad, CA 92009, USA
Tel: 760-216-7272
Fax: 760-704-6379
E-mail: [email protected]

Received Date: August 06, 2015 Accepted Date: September 09, 2015 Published Date: September 16, 2015

Citation: McCarty MF (2015) Hypothesis: Spirulina may Slow the Growth and Spread of Ovarian Cancer by Interfering with Growth Factor Activity of Lysophophatidic Acid. J Mol Genet Med 9:184. doi:10.4172/1747-0862.1000184

Copyright: © 2015 McCarty MF. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Molecular and Genetic Medicine

Abstract

Lysophosphatidic acid (LPA) has emerged as a key autocrine growth factor for most ovarian cancers, promoting their proliferation, survival, invasiveness, dissemination within the peritoneal cavity, and angiogenic capacity. Effective LPA signaling requires activation of endosomal NADPH oxidase activity. Free bilirubin is now known to function intracellularly as a potent inhibitor of NADPH oxidase complexes. The cyanobacterial chromophore phycocyanobilin (PhyCB), via intracellular conversion to the bilirubin homolog phycocyanorubin, can likewise inhibit NADPH oxidase activity, and is orally active in this regard. The cell wall polysaccharides of cyanobacteria may also aid cancer control by activating innate immunity and inhibiting angiogenesis. Hence, consumption of edible cyanobacteria such as spirulina may have potential for slowing the growth and spread of ovarian cancer – as it has recently been shown to do with a human pancreatic adenocarcinoma.

Keywords

Lysophosphatidic acid; Ovarian cancer; NADPH oxidase; Spirulina; Phycocaynobilin

Lysophosphatidic Acid – a Key Autocrine Growth Factor for Ovarian Cancer

Lysophosphatic acid (LPA) is produced by most ovarian cancer cells lines, and acts as an autocrine growth factor via its receptors LPA2 and LPA3 [1-5]. Stimulation of these receptors, linked to several heterotrimeric G proteins, promotes the phosphorylation of Akt1, ERK, EGFR, and STAT3, cox-2 expression, and the transcriptional activity of NF-kappaB and HIF-1alpha [6-11]. These effects stimulate proliferation, inhibit apoptosis, enable release of ovarian cancer cells into the peritoneal fluid by suppressing E-cadherin expression, promote invasion by inducing matrix proteases, and enhance angiogenesis by increasing the production of VEGF [5,12-19]. Studies with human ovarian cancers xenografted in nude mice demonstrate that interference with LPA signaling (via silent RNA knockdown of LPA receptors, or via transfection with an enzyme that cleaves LPA) markedly slows the spread of these cancers [13,20] – implying that LPA is an important growth factor for ovarian cancer in vivo. Levels of LPA in plasma and in peritoneal fluid are markedly higher in ovarian cancer patients than in healthy controls [21-23]. Intraperitoneal levels are highest – in part because peritoneal mesothelium also can make LPA [24] – and likely promote the formation of malignant ascites.

NADPH Oxidase Mediates LPA Signaling

Recent research indicates that stimulation of NADPH oxidase activity within endosomes plays a critical role in transmitting the signals triggered by LPA receptors [25,26]. Thus, the NADPH oxidase inhibitor DPI blocks the ability of LPA to promote phosphorylation of Akt and ERK, to activate NF-kappaB, and to stimulate proliferation [25]. Interaction of LPA with its receptors induces the internalization of these receptors into endosomes, and the activated receptors stimulate local NADPH oxidase activity that generates hydrogen peroxide within these endosomes; this leads to cysteine sulfenic acid formation in neighboring proteins that may be required for optimal LPA receptor activity [26]. N-acetylcysteine mimics the inhibitory effects of DPI [25], presumably by reversing the oxidation of protein cysteine groups [26-28]. The NADPH oxidase inhibitor apocynin, as well as a cell permeable form of catalase, likewise inhibited LPAmediated Akt phosphorylation [25]. Other studies with ovarian cancer cells lines have found that DPI promotes apoptosis, and decreases expression of HIF-1alpha and of VEGF [29,30]. Knockdown of the NADPH oxidase component Nox4 – the expression of which is increased in many of these cell lines – exerts similar effects [29].

Phycocyanobilin May Aid Ovarian Cancer Control by Suppressing NADPH Oxidase Activity

These considerations suggest that agents which can safely inhibit NADPH oxidase activity may have important potential for slowing the growth and spread of many ovarian cancers. Free intracellular bilirubin, generated via heme oxygenase activity, functions physiologically as an inhibitor of NAPDH oxidase complexes [31-34]. Although bilirubin is too insoluble to be useful as an orally administrable drug, its chemical relative phycocyanobilin (PhyCB), a prominent light-harvesting chromophore in edible cyanobacteria such as spirulina, shares the ability of bilirubin to inhibit NADPH oxidase activity [35,36]. This likely reflects the fact that PhyCB, a metabolite of biliverdin, can be converted intracellularly by biliverdin reductase to the bilirubin homolog phycocynorubin [35,37]. Moreover, spirulina and PhyCB-enriched spirulina extracts exert marked antiinflammatory/ antioxidant effects in rodent studies, suggesting that PhyCB can inhibit NADPH oxidase after oral administration [38]. Hence, oral consumption of adequate amounts of spirulina, or of PhyCB-enriched spirulina extracts, may have clinical potential for treatment of ovarian cancers. In this regard, dietary spirulina has been reported to slow the growth of a human pancreatic cancer in nude mice by about 60% [39]; notably, NADPH oxidase activity has been found to be elevated and to exert pro-growth, pro-survival effects in pancreatic cancer cells lines [40-44].

The cell wall polysaccharides of spirulina also may have potential for aiding cancer control, as they can interact with toll receptors to boost innate immunity, while also impeding angiogenesis [45,46].

As a proviso, it should be noted that spirulina probably should not be administered in conjunction with taxane chemotherapy, as the killing mechanism of these drugs appears to be contingent on NADPH oxidase activation [47-50]. On the other hand, in light of evidence that LPA signaling renders ovarian cancer cells relatively resistant to apoptosis induction by platinum drugs and doxorubicin, it is conceivable that NADPH oxidase inhibition could boost responsiveness to these drugs; however, there appears to be no direct evidence for this [51-54]. In rodents, dietary spirulina has been reported to provide protection from the cardiotoxicity of doxorubicin and the nephrotoxicity of cisplatin [55,56].

References

Select your language of interest to view the total content in your interested language
Post your comment

Share This Article

Relevant Topics

Recommended Conferences

  • 3rd Antibodies and Bio Therapeutics Congress & B2B
    November 08-09, 2017 Las Vegas, Nevada, USA
  • 19th World Congress on Biotechnology
    November 13-14, 2017 Osaka, Japan
  • 4th World Conference on Synthetic Biology and Genetic Engineering
    November 9-10, 2017 Singapore City, Singapore

Article Usage

  • Total views: 8349
  • [From(publication date):
    December-2015 - Oct 17, 2017]
  • Breakdown by view type
  • HTML page views : 8165
  • PDF downloads :184
 

Post your comment

captcha   Reload  Can't read the image? click here to refresh

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords