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.
Highlights
Cancer is a major cause of death worldwide
HCT 116 and CCRF-CEM cells were more sensitive to capsaicin and piperine than the P-gp overexpressing Caco-2 and CEM/ADR 5000 cell lines, implying than the P-gp overexpressing
Concentrations of doxorubicin and capsaicin or piperine are plotted on the x- or y-axis corresponding concentrations of doxorubicin and capsaicin or piperine are plotted on the x- or y-axis corresponding to (CDox, 0) and (0, CSM ), respectively
Summary
Cancer is a major cause of death worldwide. It is characterized by uncontrolled cell division, dedifferentiation of a normal cell, and metastatic growth. Researchers have concluded that tumorigenesis in humans is a multistep process with genetic alterations that drive the transformation of normal human cells into highly malignant derivatives [1] Anticancer drugs, such as doxorubicin, vinblastine, vincristine, epirubicin, etoposide, and imatinib, are widely used in chemotherapy [2]. Multidrug resistance is the phenomenon by which cancer cells, after being exposed to one anticancer drug, develop resistance to various other anticancer drugs that are structurally and functionally different from the initial drug. Drug efflux depends on transporters that are located in the outer biomembrane of cancer cells. Such agents are or by co-administration of substances inhibit ABC transporters Such drugs agentsand are eventually known as known as chemosensitizers since they that can reverse resistance to anticancer chemosensitizers since they can reverse resistance to anticancer drugs and eventually re-sensitize the re-sensitize the cancer cells to anticancer drugs [7]. Which do not overexpress P-gp, were used as controls
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
