The incidence of deadly diseases globally is disturbing, which has geared a number of scientists into research on various causes of these diseases. One of the deadliest diseases currently killing humans and even animals is cancer. Cancer is a broad group of various diseases involving unregulated abnormal cell growth, develops in almost any organ or tissue and it occurs in many forms of over 200 different types (Anand et al., 2008).
Leukemia, one of the most common forms of cancer in infants and adults, is a malignant clonal disorder characterized by alterations and low production of healthy hematopoietic cells, this alteration inhibits differentiation of cells and induces proliferation and accumulation of immature cells (blasts) (Parikh, Jabbour and Koller, 2011). The accumulation of blasts begins in bone marrow, but in most cases quickly builds up in the blood, and sometimes spreads to other parts of the body such as the lymph nodes, spleen, liver, testes, and the central nervous system (Ferrara and Schiffer, 2013).
Generally, in cancer, the bone marrow microenvironment becomes immunosuppressive and plays a crucial role in development and progression of the disease. Immune suppression is caused by a limitation in proinflammatory cytokine production, inhibition of activated immune cells, and generation or expansion of immunosuppressive cell types such as myeloid-derived suppressor cells (Bianchi et al., 2011;Schouppe et al., 2012)
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that regulate immune responses in healthy individuals and in the context of various diseases (Marvel and Gabrilovich, 2015;Ortiz et al., 2014). Ordinarily, immature myeloid cells formed in the bone marrow differentiate to dendritic cells, macrophages and neutrophils. However, under chronic inflammatory circumstances or cancer, myeloid cells differentiation is skewed on the way to the expansion of MDSCs. These MDSCs can infiltrate inflammatory sites and tumors, where they stop immune responses by inhibiting T lymphocytes and NK cells. Therefore, they may become a key therapeutic target (Bronte et al., 2016). Inflammatory environments have been shown to induce MDSCs development and accumulation. Indeed, IL-6, VEGF (vascular endothelial growth factor) and MCF (macrophage colony factor) all promote the development of MDSC populations by activating the STAT3 (signal transducers and activators of transcription family3) pathway. IL-4 and GM-CSF, on the other hand, can inhibit MDSC function by shifting them into mature dendritic cells (Tamadaho, Hoerauf and Layland, 2017).
In human or murine models of disease, MDSCs have been shown to have roles in cancer, bacterial and parasitic infections, acute and chronic inflammation (Tamadaho, Hoerauf and Layland, 2017) and can support tumor growth through alteration in the tumor microenvironment (Marvel and Gabrilovich, 2015;Ortizet al., 2014).
Several types of treatment may be used for people with leukemia. Doxorubicin Hydrochloride has produced significant therapeutic responses in carcinoma of the breast, lung and ovary, acute lymphocytic leukemia and acute myeloid leukemia (Kumar et al., 2014). The most dangerous side effects of doxorubicin are cardiomyopathy leading to congestive heart failure, typhlitis (an acute life-threatening infection of the bowel), fever, cough and congestion, or other signs of infection such as unusual bleeding; bloody stools and bloody vomiting (Carvalho et al., 2009).
Because of these drugs adverse side effects, researches are focusing on phytomedicines that seem to have anti-cancer and immune system enhancing activity. Phytomedicines are believed to have benefits over conventional drugs and are regaining interest in current research (Al-Asmari et al., 2015).
Moringa Oleifera (MO) is one of the best known and most widely distributed small native tree. It is now indigenous to many regions in North West India, Africa, Arabia, South East Asia, the Pacific and Caribbean Islands and South America. By tradition, besides being a daily used vegetable between people of these regions, it is also widely known and used for its health benefits (Al-Asmariet al., 2015).
Several phytochemical compounds have been isolated from MO such as quercetin, flavonoids, kaempferol, anthocyanins, carotenoids, vitamins, minerals, amino acids, sterols, glycosides, and alkaloids. Also, it contains unique group of compounds called glucosinolates and isothiocyanates which have long been known for their bactericidal, nematocidal, fungicidal, allelopathic properties and cancer chemo-protectivity (Bennett et al., 2003;Fahey, Zalcmann and Talalay, 2001)..
(Hamza, 2010) discovered that the Moringa Oleifera seed extract exhibited antifibrotic effects on liver fibrosis in rats. Also, it was found to have blood pressure lowering effect which makes it useful in a cardiovascular disorder. In addition, (Francis et al., 2004) demonstrated that Moringa Oleifera constitutes can be used for the treatment of diabetes mellitus by triggering insulin release from the rodent pancreatic cell. In addition, Moringa fruit has been found to lower cholesterol to phospholipid ratio, atherogenic index lipid and reduced the lipid profile of liver, heart, and aorta in hypercholesteremic rabbits (Mehta et al., 2003). Moringa Oleifera leaves have been described to demonstrate antioxidant activity due to its high amount of polyphenols (Verma et al., 2009). Additionally, (Lipipun et al., 2003) illustrated that Moringa Oleifera have antibacterial activity and are rich in antimicrobial agents.
Interestingly, (Bharali, Tabassum and Azad, 2003) presented evidence on the function of niazimicin (one of the Moringa Oleifera components), as a potent anti-tumor promoter. More to the point, (Al-Asmariet al., 2015) demonstrated that Moringa Oleifera extracts act as an anti-cancer agent by decreasing cell mortality and colony formation in colorectal and breast cancer cell lines. In addition, seed extract of Moringa Oleifera have been demonstrated to prevent skin tumors in mice (Bharali, Tabassum and Azad, 2003). Moreover, (Abd-Rabou et al., 2017;Abdellatef et al., 2010) established that Moringa Oleifera roots were active against leukemia cells in vitro and could be used as natural antitumor medicines. Additionally, MO leaves extract showed a great cytotoxic effect for tumor cells, strongly suggesting that it could be an ideal anticancer therapeutic candidate specific to cancer cells (Jung, 2014).
The present work aims to evaluate the potential role of Myeloid-derived suppressor cells in progression of benzene-induced leukemia and the possible role of Moringa Oleifera in enhancing the therapeutic action and minimizing the adverse side effects of Doxorubicin Hydrochloride