Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism

Marie-France Penet, Balaji Krishnamachary, Flonne Wildes, Yelena Mironchik, Delia Mezzanzanica, Franca Podo, Max de Reggi, Bouchra Gharib, Zaver M. Bhujwalla

Research output: Contribution to journalArticle

Abstract

Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here, we have assessed the effect of pantethine on tumor growth and metabolism using magnetic resonance imaging and high-resolution proton magnetic resonance spectroscopy (MRS) in a model of ovarian cancer. To evaluate treatment strategies, it is important to use models that closely mimic tumor growth in humans. Therefore, we used an orthotopic model of ovarian cancer where a piece of tumor tissue, derived from an ovarian tumor xenograft, is engrafted directly onto the ovary of female mice, to maintain the tumor physiological environment. Treatment with pantethine, the precursor of vitamin B5 and active moiety of coenzyme A, was started when tumors were ~100 mm(3) and consisted of a daily i.p. injection of 750 mg/kg in saline. Under these conditions, no side effects were observed. High-resolution (1)H MRS was performed on treated and control tumor extracts. A dual-phase extraction method based on methanol/chloroform/water was used to obtain lipid and water-soluble fractions from the tumors. We also investigated effects on metastases and ascites formation. Pantethine treatment resulted in slower tumor progression, decreased levels of phosphocholine and phosphatidylcholine, and reduced metastases and ascites occurrence. In conclusion, pantethine represents a novel potential, well-tolerated, therapeutic tool in patients with ovarian cancer. Further in vivo preclinical studies are needed to confirm the beneficial role of pantethine and to better understand its mechanism of action.

Original languageEnglish
Pages (from-to)244
JournalFrontiers in Oncology
Volume6
DOIs
Publication statusPublished - 2016

Fingerprint

Choline
Neoplasms
Ovarian Neoplasms
Ascites
pantethine
Pantothenic Acid
Neoplasm Metastasis
Therapeutics
Phosphorylcholine
Water
Coenzyme A
Growth
Chloroform
Phosphatidylcholines
Developed Countries
Heterografts
Methanol
Cause of Death
Ovary
Magnetic Resonance Spectroscopy

Keywords

  • Journal Article

Cite this

Penet, M-F., Krishnamachary, B., Wildes, F., Mironchik, Y., Mezzanzanica, D., Podo, F., ... Bhujwalla, Z. M. (2016). Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism. Frontiers in Oncology, 6, 244. https://doi.org/10.3389/fonc.2016.00244

Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism. / Penet, Marie-France; Krishnamachary, Balaji; Wildes, Flonne; Mironchik, Yelena; Mezzanzanica, Delia; Podo, Franca; de Reggi, Max; Gharib, Bouchra; Bhujwalla, Zaver M.

In: Frontiers in Oncology, Vol. 6, 2016, p. 244.

Research output: Contribution to journalArticle

Penet, M-F, Krishnamachary, B, Wildes, F, Mironchik, Y, Mezzanzanica, D, Podo, F, de Reggi, M, Gharib, B & Bhujwalla, ZM 2016, 'Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism', Frontiers in Oncology, vol. 6, pp. 244. https://doi.org/10.3389/fonc.2016.00244
Penet, Marie-France ; Krishnamachary, Balaji ; Wildes, Flonne ; Mironchik, Yelena ; Mezzanzanica, Delia ; Podo, Franca ; de Reggi, Max ; Gharib, Bouchra ; Bhujwalla, Zaver M. / Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism. In: Frontiers in Oncology. 2016 ; Vol. 6. pp. 244.
@article{81257643ba934c579258d1d9d3effd27,
title = "Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism",
abstract = "Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here, we have assessed the effect of pantethine on tumor growth and metabolism using magnetic resonance imaging and high-resolution proton magnetic resonance spectroscopy (MRS) in a model of ovarian cancer. To evaluate treatment strategies, it is important to use models that closely mimic tumor growth in humans. Therefore, we used an orthotopic model of ovarian cancer where a piece of tumor tissue, derived from an ovarian tumor xenograft, is engrafted directly onto the ovary of female mice, to maintain the tumor physiological environment. Treatment with pantethine, the precursor of vitamin B5 and active moiety of coenzyme A, was started when tumors were ~100 mm(3) and consisted of a daily i.p. injection of 750 mg/kg in saline. Under these conditions, no side effects were observed. High-resolution (1)H MRS was performed on treated and control tumor extracts. A dual-phase extraction method based on methanol/chloroform/water was used to obtain lipid and water-soluble fractions from the tumors. We also investigated effects on metastases and ascites formation. Pantethine treatment resulted in slower tumor progression, decreased levels of phosphocholine and phosphatidylcholine, and reduced metastases and ascites occurrence. In conclusion, pantethine represents a novel potential, well-tolerated, therapeutic tool in patients with ovarian cancer. Further in vivo preclinical studies are needed to confirm the beneficial role of pantethine and to better understand its mechanism of action.",
keywords = "Journal Article",
author = "Marie-France Penet and Balaji Krishnamachary and Flonne Wildes and Yelena Mironchik and Delia Mezzanzanica and Franca Podo and {de Reggi}, Max and Bouchra Gharib and Bhujwalla, {Zaver M.}",
year = "2016",
doi = "10.3389/fonc.2016.00244",
language = "English",
volume = "6",
pages = "244",
journal = "Frontiers in Oncology",
issn = "2234-943X",
publisher = "Frontiers Media S. A.",

}

TY - JOUR

T1 - Effect of Pantethine on Ovarian Tumor Progression and Choline Metabolism

AU - Penet, Marie-France

AU - Krishnamachary, Balaji

AU - Wildes, Flonne

AU - Mironchik, Yelena

AU - Mezzanzanica, Delia

AU - Podo, Franca

AU - de Reggi, Max

AU - Gharib, Bouchra

AU - Bhujwalla, Zaver M.

PY - 2016

Y1 - 2016

N2 - Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here, we have assessed the effect of pantethine on tumor growth and metabolism using magnetic resonance imaging and high-resolution proton magnetic resonance spectroscopy (MRS) in a model of ovarian cancer. To evaluate treatment strategies, it is important to use models that closely mimic tumor growth in humans. Therefore, we used an orthotopic model of ovarian cancer where a piece of tumor tissue, derived from an ovarian tumor xenograft, is engrafted directly onto the ovary of female mice, to maintain the tumor physiological environment. Treatment with pantethine, the precursor of vitamin B5 and active moiety of coenzyme A, was started when tumors were ~100 mm(3) and consisted of a daily i.p. injection of 750 mg/kg in saline. Under these conditions, no side effects were observed. High-resolution (1)H MRS was performed on treated and control tumor extracts. A dual-phase extraction method based on methanol/chloroform/water was used to obtain lipid and water-soluble fractions from the tumors. We also investigated effects on metastases and ascites formation. Pantethine treatment resulted in slower tumor progression, decreased levels of phosphocholine and phosphatidylcholine, and reduced metastases and ascites occurrence. In conclusion, pantethine represents a novel potential, well-tolerated, therapeutic tool in patients with ovarian cancer. Further in vivo preclinical studies are needed to confirm the beneficial role of pantethine and to better understand its mechanism of action.

AB - Epithelial ovarian cancer remains the leading cause of death from gynecologic malignancy among women in developed countries. New therapeutic strategies evaluated with relevant preclinical models are urgently needed to improve survival rates. Here, we have assessed the effect of pantethine on tumor growth and metabolism using magnetic resonance imaging and high-resolution proton magnetic resonance spectroscopy (MRS) in a model of ovarian cancer. To evaluate treatment strategies, it is important to use models that closely mimic tumor growth in humans. Therefore, we used an orthotopic model of ovarian cancer where a piece of tumor tissue, derived from an ovarian tumor xenograft, is engrafted directly onto the ovary of female mice, to maintain the tumor physiological environment. Treatment with pantethine, the precursor of vitamin B5 and active moiety of coenzyme A, was started when tumors were ~100 mm(3) and consisted of a daily i.p. injection of 750 mg/kg in saline. Under these conditions, no side effects were observed. High-resolution (1)H MRS was performed on treated and control tumor extracts. A dual-phase extraction method based on methanol/chloroform/water was used to obtain lipid and water-soluble fractions from the tumors. We also investigated effects on metastases and ascites formation. Pantethine treatment resulted in slower tumor progression, decreased levels of phosphocholine and phosphatidylcholine, and reduced metastases and ascites occurrence. In conclusion, pantethine represents a novel potential, well-tolerated, therapeutic tool in patients with ovarian cancer. Further in vivo preclinical studies are needed to confirm the beneficial role of pantethine and to better understand its mechanism of action.

KW - Journal Article

U2 - 10.3389/fonc.2016.00244

DO - 10.3389/fonc.2016.00244

M3 - Article

C2 - 27900284

VL - 6

SP - 244

JO - Frontiers in Oncology

JF - Frontiers in Oncology

SN - 2234-943X

ER -