Abstract

Doxorubicin (DOX) is a well-known chemotherapeutic agent extensively applied in the field of cancer therapy. However, similar to other chemotherapeutic agents such as cisplatin, paclitaxel, docetaxel, etoposide and oxaliplatin, cancer cells are able to obtain chemoresistance that limits DOX efficacy. In respect to dose-dependent side effect of DOX, enhancing its dosage is not recommended for effective cancer chemotherapy. Therefore, different strategies have been considered for reversing DOX resistance and diminishing its side effects. Phytochemical are potential candidates in this case due to their great pharmacological activities. Curcumin is a potential antitumor phytochemical isolated from Curcuma longa with capacity of suppressing cancer metastasis and proliferation and affecting molecular pathways. Experiments have demonstrated the potential of curcumin for inhibiting chemoresistance by downregulating oncogene pathways such as MMP-2, TGF-β, EMT, PI3K/Akt, NF-κB and AP-1. Furthermore, coadministration of curcumin and DOX potentiates apoptosis induction in cancer cells. In light of this, nanoplatforms have been employed for codelivery of curcumin and DOX. This results in promoting the bioavailability and internalization of the aforementioned active compounds in cancer cells and, consequently, enhancing their antitumor activity. Noteworthy, curcumin has been applied for reducing adverse effects of DOX on normal cells and tissues via reducing inflammation, oxidative stress and apoptosis. The current review highlights the anticancer mechanism, side effects and codelivery of curcumin and DOX via nanovehicles.

Highlights

  • The necessity for having a new approach in chemotherapy is due to an emerging phenomenon, known as “chemoresistance” [1]

  • Curcumin can be coapplied with DOX in promoting its antitumor activity

  • The metastasis of cancer cells is negatively affected by curcumin in promoting DOX efficacy via MMP-2 downregulation and Tissue inhibitors of metalloproteinases (TIMPs)-1 upregulation

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Summary

Introduction

The necessity for having a new approach in chemotherapy is due to an emerging phenomenon, known as “chemoresistance” [1]. Increasing evidence demonstrates that phytochemicals, due to their excellent antitumor activity, can be considered as potential agents for coadministration with chemotherapeutic agents in cancer therapy [4,5]. Phytochemicals impair proliferation and metastasis of cancer cells, and sensitize cancer cells to apoptosis and DNA damage caused by chemotherapeutic agents [6,7,8]. This polychemotherapy with natural compounds is of importance in reversing chemoresistance. Potentiating antitumor activity of doxorubicin against cancer cells, reversing chemoresistance and nanocarriers for codelivery of curcumin and doxorubicin are described in this review article based on newly published articles

Curcumin
Antitumor Activity of Curcumin
Curcumin in Cancer Chemotherapy
Doxorubicin
Apoptosis Induction
Metastasis Inhibition
Potential Mechanisms of DOX Resistance
Curcumin in Reversing DOX Resistance
Impact on Adverse Effects
Codelivery via Biological Nanovehicles
Findings
Conclusions and Remarks
Full Text
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