In Search of Effective Anticancer Agents-Novel Sugar Esters Based on Polyhydroxyalkanoate Monomers

• Published in: International journal of molecular sciences Vol. 22; no. 13; p. 7238
• Main Authors: Snoch, Wojciech, Wnuk, Dawid, Witko, Tomasz, Staroń, Jakub, Bojarski, Andrzej J, Jarek, Ewelina, Plou, Francisco J, Guzik, Maciej
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.07.2021; MDPI
• Subjects: Actin; anticancer agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Biocompatibility; Biological activity; Cancer therapies; Carbon; Cell division; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; chemical modifications; Cytotoxicity; Depolymerization; Drug Discovery; Drug Screening Assays, Antitumor; Esters; Esters - chemistry; Esters - pharmacology; Fatty acids; Female; Filaments; fluorination; Glucose; Humans; Hydrophobicity; Intermediate Filaments - drug effects; Intermediate Filaments - ultrastructure; Lactose; Male; Melanoma; Metastases; Microtubules; Pharmaceutical industry; Polyhydroxyalkanoates; Polyhydroxyalkanoates - chemistry; Polyhydroxyalkanoates - pharmacology; Polyhydroxyalkanoic acid; Prostate cancer; Skin cancer; Solvents; Structure-Activity Relationship; sugar esters; Sugars - chemistry; Sugars - pharmacology; Surfactants; Tumor cell lines; United States > US; prostate cancer; sugar esters; chemical modifications; fluorination; melanoma; polyhydroxyalkanoates; anticancer agents
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22137238

Cancer is one of the deadliest illness globally. Searching for new solutions in cancer treatments is essential because commonly used mixed, targeted and personalized therapies are sometimes not sufficient or are too expensive for common patients. Sugar fatty acid esters (SFAEs) are already well-known as promising candidates for an alternative medical tool. The manuscript brings the reader closer to methods of obtaining various SFAEs using combined biological, chemical and enzymatic methods. It presents how modification of SFAE's hydrophobic chains can influence their cytotoxicity against human skin melanoma and prostate cancer cell lines. The compound's cytotoxicity was determined by an MTT assay, which followed an assessment of SFAEs' potential metastatic properties in concentrations below IC values. Despite relatively high IC values (63.3-1737.6 μM) of the newly synthesized SFAE, they can compete with other sugar esters already described in the literature. The chosen bioactives caused low polymerization of microtubules and the depolymerization of actin filaments in nontoxic levels, which suggest an apoptotic rather than metastatic process. Altogether, cancer cells showed no propensity for metastasis after treating them with SFAE. They confirmed that lactose-based compounds seem the most promising surfactants among tested sugar esters. This manuscript creates a benchmark for creation of novel anticancer agents based on 3-hydroxylated fatty acids of bacterial origin.