Breast cancer ranks second among the causes of cancer-related deaths in women. In spite of the recent advances achieved in the diagnosis and treatment of breast cancer, further study is required to overcome the risk of cancer resistance to treatment and thereby improve the prognosis of individuals with advanced-stage breast cancer. The existence of a hypoxic microenvironment is a well-known event in the development of mutagenesis and rapid proliferation of cancer cells. Tumor cells, purposefully cause local hypoxia in order to induce angiogenesis and growth factors that promote tumor growth and metastatic characteristics, while healthy tissue surrounding the tumor suffers damage or mutate. It has been found that these settings with low oxygen levels cause immunosuppression and a lack of immune surveillance by reducing the activation and recruitment of tumor infiltrating leukocytes (TILs). The immune system is further suppressed by hypoxic tumor endothelium through a variety of ways, which creates an immunosuppressive milieu in the tumor microenvironment. Non responsiveness of tumor endothelium to inflammatory signals or endothelial anergy exclude effector T cells from the tumor milieu. Expression of endothelial specific antigens and immunoinhibitory molecules like Programmed death ligand 1,2 (PDL–1, 2) and T cell immunoglobulin and mucin-domain containing-3 (TIM-3) by tumor endothelium adds fuel to the fire by inhibiting T lymphocytes while promoting regulatory T cells. The hypoxic microenvironment in turn recruits Myeloid Derived Suppressor Cells (MDSCs), Tumor Associated Macrophages (TAMs) and T regulatory cells (Treg). The structure and function of newly generated blood vessels within tumors, on the other hand, are aberrant, lacking the specific organization of normal tissue vasculature. Vascular normalisation may work for a variety of tumour types and show to be an advantageous complement to immunotherapy for improving tumour access. By enhancing immune response in the hypoxic tumor microenvironment, via immune-herbal therapeutic and immune-nutraceuticals based approaches that leverage immunological evasion of tumor, will be briefly reviewed in this article. Whether these tactics may be the game changer for emerging immunological switch point to attenuate the breast cancer growth and prevent metastatic cell division, is the key concern of the current study.

Introduction: Isodeoxyelephantopin (C19H20O6), plant-derived sesquiterpene, extracted from Elephantopus Scaber Linn., have tremendous contributions in inhibiting the proliferation and metastasis of cancer cells. Materials and Methods: The cell viability assay was shown to be procured half-maximal inhibitory concentration of isodeoxyelephantopin on the MDA-MB-231cell line. Apoptosis was screened by AO/ EB staining and it was confirmed by annexin V staining. The DNA damaging property of IDOE was examined by comet assay. The cell cycle arrest determined using flow cytometry analysis and the growth inhibition due to the modulation of cell cycle regulatory protein p53 were substantiated by RT PCR. Scratch wound migratory assay was done to evaluate the migratory effect of IDOE on the MDA-MB-231 cell line. RT-PCR analysis showed that expression of MMP-2/9 was inhibited by IDOE treatment. Result: Anti-proliferative and anti-migratory effect of IDOE was determined by cell cycle analysis and annexin v staining. Cells were arrested in the G2/M phase and it is due to the modulation of cell cycle regulatory protein p53. The mRNA level expression studies of matrix metalloproteinases, MMP-2/9 provide supporting data to prove the anti-migratory property.