Adjuvant chemotherapy with melatonin for targeting human cancers: A review

Abstract

Melatonin is a multifunctional hormone that has long been known for its antitumoral effects. An advantage of the application of melatonin in cancer therapy is its ability to differentially influence tumors from normal cells. In this review, the roles of melatonin adjuvant therapy in human cancer are discussed. Combination of melatonin with chemotherapy could provide synergistic antitumoral outcomes and resolve drug resistance in affected patients. This combination reduces the dosage for chemotherapeutic agents with the subsequent attenuation of side effects related to these drugs on normal cells around tumor and on healthy organs. The combination therapy increases the rate of survival and improves the quality of life in affected patients. Cancer cell viability is reduced after application of the combinational melatonin therapy. Melatonin does all these functions by adjusting the signals involved in cancer progression, re-establishing the dark/light circadian rhythm, and disrupting the redox system for cancer cells. To achieve effective therapeutic outcomes, melatonin concentration along with the time of incubation for this indoleamine needs to be adjusted. Importantly, a special focus is required to be made on choosing an appropriate chemotherapy agent for using in combination with melatonin. Because of different sensitivities of cancer cells for melatonin combination therapy, cancer-specific targeted therapy is also needed to be considered. For this review, the PubMed database was searched for relevant articles based on the quality of journals, the novelty of articles published by the journals, and the number of citations per year focusing only on human cancers.

Transforming growth factor‐β signaling: Tumorigenesis and targeting for cancer therapy

“…ECM stiffness through this signaling facilitates contacts between cancer cells with BM via β1 integrin. This interaction is for breaking the barrier (provided by the BM) and loosening adhesion of cancer cells and so promoting their further invasion (Najafi et al, 2018c;Wei et al, 2017). A point to consider is that ECM degradation induces TGF-β activity for further promotion of ECM stiffness, both of which (degradation and stiffness) contributed to the progression of the tumor.…”

“…Upon tumor progression, TGF-β would take a diverse route by promoting EMT, stimulating proliferation of CSCs and maintaining them in a quiescent state, and inducing invasion, proliferation, and metastasis of cancer cells in canonical (Smad-dependent) or noncanonical (Smad-independent) pathways. CDKs: cyclin-dependent kinases; CSCs: cancer stem cells; EMT: epithelial-mesenchymal transition; Hh: hedgehog; JNK: c-Jun amino-terminal kinase; MMP: matrix metalloproteinase; RTK: tyrosine kinase receptor; TGF-β: transforming growth factor-β metastasis (Najafi et al, 2018b). HIF-1α is also a positive stimulator of COX-2 overexpression in cancer.…”

Application of a New Validated HPLC-PDA Method for Simultaneous Determination of Curcumin and Melatonin in Hyaluronic Acid-Coated Nanoemulsions

“…4,9,10 Melatonin (MEL) has a variety of biological properties including anti-inflammatory and antioxidant activity, as well as immune system regulator. [11][12][13][14][15] In cancer cells, MEL has the capacity to induce intracellular reactive oxygen species (ROS), whose accumulation plays an upstream role in mitochondria-mediated apoptosis and autophagy. Moreover, it can act more specifically on cancer cells, but not on normal cells, showing synergistic anticancer activity and reducing undesirable side effects in several chemotherapy regimens.…”

Therapeutic effects of kaempferol affecting autophagy and endoplasmic reticulum stress

“…In other words, the harmful effects of synthetic drugs lead to the substitution of natural compounds for the remediation of a number of disorders (Azmoonfar et al, ; Farhood et al, ; Kolivand et al, ; Shabeeb et al, ). It has been shown that natural compounds derived from fruits and vegetables have various biological and therapeutic activities such as anticancer, antidiabetic, antiobesity, anti‐inflammatory, and antioxidant (Amini et al, , ; Najafi et al, , ; Shabeeb et al, ). However, among them, flavonoids are of interest and their beneficial effects are dose dependent (20–1,000 mg/day) (Scalbert & Williamson, ; Wang et al, ).…”