Adding a combination of hydroxycitrate and lipoic acid (METABLOC™) to chemotherapy improves effectiveness against tumor development: experimental results and case report

• Published in: Investigational new drugs Vol. 30; no. 1; pp. 200 - 211
• Main Authors: Guais, Adeline, Baronzio, GianFranco, Sanders, Edward, Campion, Frédéric, Mainini, Carlo, Fiorentini, Giammaria, Montagnani, Francesco, Behzadi, Mahsa, Schwartz, Laurent, Abolhassani, Mohammad
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01-02-2012; Springer Nature B.V
• Subjects: Aged, 80 and over; Animals; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bladder; Cancer therapies; Carcinoma, Lewis Lung - drug therapy; Carcinoma, Lewis Lung - metabolism; Carcinoma, Lewis Lung - pathology; Carcinoma, Pancreatic Ductal - drug therapy; Carcinoma, Pancreatic Ductal - metabolism; Carcinoma, Pancreatic Ductal - secondary; Case reports; Cell Line, Tumor; Chemotherapy; Cisplatin - administration & dosage; Citrates - administration & dosage; Cytotoxicity; Dehydrogenases; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Drugs; Energy Metabolism - drug effects; Enzymes; Female; Glucose; Humans; Kinases; Laboratory animals; Medicine; Medicine & Public Health; Metabolism; Methotrexate - administration & dosage; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Oncology; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Pharmacology; Pharmacology/Toxicology; Preclinical Studies; Studies; Thioctic Acid - administration & dosage; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Tumors; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Europe; Pyruvate dehydrogenase; Metabolic therapy; ATP citrate lyase
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-010-9552-x

Summary
Altered metabolism of cancer first highlighted by Otto Warburg has a long history. Although ignored for a considerable amount of time, it is now receiving substantial attention. We recently published results obtained with a combination of two drugs, lipoic acid and hydroxycitrate, targeting metabolic enzymes particularly affected in cancer: ATP citrate lyase and pyruvate dehydrogenase kinase. This treatment was as efficient as chemotherapy in the three mouse cancer models that were tested. In this work, we asked if our drug combination could be used in conjunction with standard cytotoxic chemotherapy, in particular cisplatin, to improve basic protocol efficacy. A combination of lipoic acid and hydroxycitrate was administered to mice implanted with syngeneic cancer cells, LL/2 lung carcinoma and MBT-2 bladder carcinoma, concommitantly with classical chemotherapy (cisplatin or methotrexate). We demonstrate that the triple combination lipoic acid + hydroxycitrate + cisplatin or methotrexate is more efficient than cisplatin or methotrexate used individually or the combination of lipoic acid and hydroxycitrate administered alone. Of particular note are the results obtained in the treatment of an 80 year-old female who presented with ductal adenocarcinoma of the pancreas accompanied by liver metastases. A treatment course using gemcitabine plus α-lipoic acid and hydroxycitrate gave highly promising results. The in vivo data, coupled with the case study results, suggest a possible advantage in using a treatment targeted at cancer metabolism in association with classical chemotherapy.