Capsaicin and Piperine Can Overcome Multidrug Resistance in Cancer Cells to Doxorubicin.

Abstract

BACKGROUND:

Multidrug resistance (MDR) can develop in cancer cells after treatment with anticancer drugs, mainly due to the overexpression of the ATP-binding cassette (ABC) transporters. We analyzed the ability of two pungent-tasting alkaloids-capsaicin and piperine from Capsicum frutescens and Piper nigrum, respectively-to reverse multidrug resistance in the cancer cell lines Caco-2 and CEM/ADR 5000, which overexpress P-glycoprotein (P-gp) and other ABC transporters.

METHODS:

The MTT assay was first used to determine the cytotoxicity of doxorubicin, the alkaloids, and digitonin alone, and then their combinations. Furthermore, rhodamine (Rho) 123 and calcein-AM were used to detect the effects of alkaloids on the activity of P-gp.

RESULTS:

Capsaicin and piperine synergistically enhanced the cytotoxicity of doxorubicin in Caco-2 and CEM/ADR 5000 cells. Furthermore, capsaicin and piperine increased the intracellular accumulation of the fluorescent P-glycoprotein (P-gp) substrates rhodamine and calcein and inhibited their efflux from the MDR cell lines.

CONCLUSION:

Our study has demonstrated that capsaicin and piperine are P-gp substrates and have potential chemosensitizing activity, which might be interesting for the development of novel modulators of multidrug resistance.

• Authors: Hanmei Li, Sonja Krstin, Shihui Wang, Michael Wink
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 23 Issue 3 (Mar 02 2018) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 29498663 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Alkaloids
• Antibiotics, Antineoplastic
• Antineoplastic Agents, Phytogenic
• Benzodioxoles
• Drug Combinations
• Fluoresceins
• Piperidines
• Polyunsaturated Alkamides
• calcein AM
• Rhodamine 123
• Doxorubicin
• Capsaicin
• piperine

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (antagonists & inhibitors, genetics, metabolism)
• Alkaloids (isolation & purification, pharmacology)
• Antibiotics, Antineoplastic (pharmacology)
• Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology)
• Benzodioxoles (isolation & purification, pharmacology)
• Biological Transport (drug effects)
• Caco-2 Cells
• Capsaicin (isolation & purification, pharmacology)
• Capsicum (chemistry)
• Cell Line, Tumor
• Doxorubicin (pharmacology)
• Drug Combinations
• Drug Resistance, Multiple (drug effects, genetics)
• Drug Resistance, Neoplasm (drug effects, genetics)
• Drug Synergism
• Fluoresceins (metabolism)
• Gene Expression
• HCT116 Cells
• Humans
• Piper nigrum (chemistry)
• Piperidines (isolation & purification, pharmacology)
• Polyunsaturated Alkamides (isolation & purification, pharmacology)
• Rhodamine 123 (metabolism)