Abstract:
Breast cancer is the most frequently diagnosed cancer among females in Pakistan. According to the South Asian data of population based cancer registry, Pakistan has 69 per 100,000 age standardized rate, the highest among South Asia, of breast cancer. Although many anti-cancer drugs have been developed, the need for more efficacious and targeted therapy persists. Chemoprevention and therapy of cancer by use of natural agents such as flavonoids that can inhibit or suppress the hallmarks of cancer has gained attention to combat the dogma of worldwide increasing cancer cases. Major steps involved in cancer progression are cell growth and proliferation which are regulated by phosphorylation of serine, threonine and tyrosine residues. These reactions are catalyzed by protein kinases such as PKCs, which results in triggering large number of cascades involved in signaling pathways. PKC epsilon, a novel calcium independent isoform, has been reported to be involved in aggressive and invasive breast cancer. The possibility of use of citrus flavonoids as anti-carcinogenic agent lies in their promising potential of inhibiting various PKs, thereby suppressing the event of cell growth and proliferation. In this study we investigated the effect of tetrahydroxyflavanone on cell viability, cell growth, proliferation, migration and the apoptosis of MCF-7 and MDA-MB-231 cell. Moreover, a thorough evaluation of the binding ability of tetrahydroxyflavanone with PKCε and KLF7 is undertaken. Molecular docking results revealed a strong binding between tetrahydroxyflavanone with PKCε and KLF7. Cell culture results indicated that tetrahydroxyflavanone markedly inhibited cell growth ability of both cells. In addition, a dose- dependent inhibition of colony formation ability of both cells was observed. In response to tetrahydroxyflavanone, an increase in the early and late apoptotic cells was also observed. Taken together, this data provide scientific evidence for the anti-cancer potential of tetrahydroxyflavanone against breast cancer and hence, can be proposed as a natural therapeutic agent against breast cancer.
