Curcumin circumvent lactate-induced chemoresistance in hepatic cancer cells through modulation of hydroxycarboxylic acid receptor-1

Vivek Kumar Soni; Dhananjay Shukla; Ajay Kumar; Naveen Kumar Vishvakarma

doi:10.1016/j.biocel.2020.105752

Curcumin circumvent lactate-induced chemoresistance in hepatic cancer cells through modulation of hydroxycarboxylic acid receptor-1

Int J Biochem Cell Biol. 2020 Jun:123:105752. doi: 10.1016/j.biocel.2020.105752. Epub 2020 Apr 20.

Authors

Vivek Kumar Soni¹, Dhananjay Shukla¹, Ajay Kumar², Naveen Kumar Vishvakarma³

Affiliations

¹ Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur 495 009, Chhattisgarh, India.
² Department of Zoology, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India.
³ Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur 495 009, Chhattisgarh, India. Electronic address: [email protected].

PMID: 32325281
DOI: 10.1016/j.biocel.2020.105752

Abstract

Curcumin has been demonstrated to affect the chemoresistance in cancer cells of various origins. However, its ability to modulate lactate-induced chemoresistance remains unclear. The Present investigation demonstrates that curcumin inhibits the survival of HepG2 and HuT78 cells and can modulate chemo-susceptibility of HepG2 cells. Experimental simulation of simultaneous and pre-treatment suggest cooperatively between curcumin and anticancer drugs as well as the modulation of molecular regulators. Inhibition of glucose consumption, lactate production, extracellular acidity and augmented level of Nitric oxide were observed. DAPI staining revealed hyper condensation of chromatin in curcumin-treated HepG2 cells. Curcumin also diminished the lactate-induced chemoresistance against doxorubicin in hepatic cancer cells along with down regulation of lactate receptor (hydroxycarboxylic acid receptor-1; HCAR-1/GPR81). Alteration of the extracellular milieu along with inhibited expression of genes (hif-1α, ldh-a, mct-1, mdr-1 and stat-3) and proteins (HIF-1α and HCAR-1) are indicated to be involved in curcumin-induced reversal of chemoresistance in HepG2 cells. Findings of present investigation contribute to knowledge of curcumin mediated chemosensitization and its mechanism.

Keywords: Chemoresistance; Curcumin; HCAR-1/GPR81; Lactate.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / therapeutic use
Apoptosis / drug effects
Cell Survival / drug effects
Chromatin / drug effects
Chromatin / metabolism
Cisplatin / pharmacology
Curcumin / pharmacology*
Curcumin / therapeutic use
Doxorubicin / pharmacology
Drug Resistance, Neoplasm / drug effects*
Drug Synergism
Gene Expression Regulation, Neoplastic / drug effects*
Glucose / metabolism
Hep G2 Cells
Hepatocytes / drug effects
Hepatocytes / metabolism
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / genetics
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Lactate Dehydrogenase 5 / genetics
Lactate Dehydrogenase 5 / metabolism
Lactic Acid / metabolism*
Liver Neoplasms / drug therapy*
Liver Neoplasms / genetics
Liver Neoplasms / metabolism
Monocarboxylic Acid Transporters / genetics
Monocarboxylic Acid Transporters / metabolism
Nitric Oxide / metabolism
Rats
Receptors, G-Protein-Coupled / genetics
Receptors, G-Protein-Coupled / metabolism*
STAT3 Transcription Factor / genetics
STAT3 Transcription Factor / metabolism
Symporters / genetics
Symporters / metabolism

Substances

Antineoplastic Agents
Chromatin
HCAR1 protein, human
HIF1A protein, human
Hypoxia-Inducible Factor 1, alpha Subunit
Monocarboxylic Acid Transporters
Receptors, G-Protein-Coupled
STAT3 Transcription Factor
STAT3 protein, human
Symporters
monocarboxylate transport protein 1
Nitric Oxide
Lactic Acid
Doxorubicin
Lactate Dehydrogenase 5
Curcumin
Glucose
Cisplatin