Thyroid cancer is the most common sort of endocrine-related cancer with more prevalent in women and elderly individuals which has quickly widespread expansion in worldwide over the recent decades. Common features of malignant thyroid cells are to have accelerated metabolism and increased glucose uptake to optimize their energy supply which provides a fundamental advantage for growth. In tumor cells the retaining of required energy charge for cell survival is imperative, indeed glucose transporters are enable of promoting of this task. According to this relation it has been reported the upregulation of glucose transporters in various types of cancers. Human studies indicated that poor survival can be occurred following the high levels of GLUT1 expression in tumors. GLUT-1 and GLUT3 are the glucose transporters which seems to be mainly engaged with the oncogenesis of thyroid cancer and their expression in malignant tissues is much more than in the normal one. They are promising targets for the advancement of anticancer strategies. The lack of oncosuppressors have dominant effect on the membrane expression of GLUT1 and glucose uptake. Overexpression of hypoxia inducible factors have been additionally connected with distant metastasis in thyroid cancers which mediates transcriptional regulation of glycolytic genes including GLUT1 and GLUT3. Though the physiological role of the thyroid gland is well illustrated, but the metabolic regulations in thyroid cancer remain evasive. In this study we discuss proliferation pathways of the key regulators and signaling molecules such as PI3K-Akt, HIF-1, MicroRNA, PTEN, AMPK, BRAF, c-Myc, TSH, Iodide and p53 which includes in the regulation of GLUTs in thyroid cancer cells. Incidence of deregulations in cellular energetics and metabolism are the most serious signs of cancers. In conclusion, understanding the mechanisms of glucose transportation in normal and pathologic thyroid tissues is critically important and could provide significant insights in science of diagnosis and treatment of thyroid disease.

Background Therapeutic resistance to radiation and chemotherapy is one of the major obstacles in cancer treatment. Although synthetic radiosensitizers are pragmatic solution to enhance tumor sensitivity, they pose concerns of toxicity and non-specificity. In the last decades, scientists scrutinized novel plant-derived radiosensitizers and chemosensitizers, such as flavones, owing to their substantial physiological effects like low toxicity and non-mutagenic properties on the human cells. The combination therapy with apigenin is potential candidate in cancer therapeutics. This review explicates the combinatorial strategies involving apigenin to overcome drug resistance and boost the anti-cancer properties. Methods We selected full-text English papers on international databases like PubMed, Web of Science, Google Scholar, Scopus, and ScienceDirect from 1972 up to 2020. The keywords included in the search were: Apigenin, Chemoprotective, Chemosensitizing, Side Effects, and Molecular Mechanisms. Results In this review, we focused on combination therapy, particularly with apigenin augmenting the anti-cancer effects of chemo drugs on tumor cells, reduce their side effects, subdue drug resistance, and protect healthy cells. The reviewed research data implies that these co-therapies exhibited a synergistic effect on various cancer cells, where apigenin sensitized the chemo drug through different pathways including a significant reduction in overexpressed genes, AKT phosphorylation, NFκB, inhibition of Nrf2, overexpression of caspases, up-regulation of p53 and MAPK, compared to the monotherapies. Meanwhile, contrary to the chemo drugs alone, combined treatments significantly induced apoptosis in the treated cells. Conclusion Briefly, our analysis proposed that the combination therapies with apigenin could suppress the unwanted toxicity of chemotherapeutic agents. It is believed that these expedient results may pave the path for the development of drugs with a high therapeutic index. Nevertheless, human clinical trials are a prerequisite to consider the potential use of apigenin in the prevention and treatment of various cancers. Conclusively, the clinical trials to comprehend the role of apigenin as a chemoprotective agent are still in infancy. Graphical Abstract