Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

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.

Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery

“…After its discovery, DOX was considered as the first option in treatment of cancer patients and showed promising clinical results. However, these ideal findings disappeared with development of DOX resistance [3][4][5][6].…”

Curcumin Nanoparticles as Promising Therapeutic Agents for Drug Targets

“…Hence, to treat this disease, the medical field has developed different treatment processes, chemotherapy being one of the most common treatments. According to [ 106 ], the principal for the antitumor activity of the chemotherapeutics is by triggering the apoptosis pathway, causing impairment in the microtubules and causing DNA damage of the cancer cells. However, it is being observed that the cancer cells are getting resistance to the chemotherapeutic agents, which is often called termed as “chemoresistance”.…”

“…The resistance of the cancer cells in induction of apoptosis is considered as one of the reasons of such phenomenon. Moreover, it is also observed that the chemo resistant cancer cells possess DNA protecting properties by stimulating DNA repairing pathways and thus preventing it from damage [ 106 ]. Curcumin is a phytochemical which is universally considered as a potential anticancer agent, and has been proven to provide protection to all types of cancer.…”

“…Thus, when curcumin is administered, due to its high antioxidant capacity, it reduces the oxidative stress in the body, and when co-administered with chemotherapeutic drugs, it exerts anti-tumor activity and also increases the drug sensitivity. Moreover, it hinders the colonization of cancer cells, which further provides better protection [ 106 ]. Curcumin has also been established to be effective in people suffering from colorectal cancer, and it was observed that it decreased the level of serum Tumor necrosis factor (TNF-α), as well as increased the apoptosis and also improved the overall health.…”

Small in Size, but Large in Action: microRNAs as Potential Modulators of PTEN in Breast and Lung Cancers

“…However, we are still at the beginning point, and more studies will reveal upstream mediators of the miRNA/PTEN axis [284]. Curcumin is a plant derived-natural compound derived from Curcuma longa with anti-tumor activity against breast cancer cells capable of inducing apoptosis and suppressing metastasis [285][286][287][288][289][290]. Curcumin is an important regulator of cell cycle in cancer.…”