br Introduction br Cervical cancer represents the
Cervical cancer represents the second most common cancer with 5.2 million new cases diagnosed every year and ranked fourth in mortality rate with 2.6 million deaths . World Health Organization (WHO) reports that cervical cancer deaths in under developing countries ac-count for about 90% . The current therapeutic options such as sur-gery, radio and chemotherapy are limited and often unsuccessful due to several reasons. Though the morbidity can be reduced by opting for
surgery, spreading of cancer Amiloride HCL to healthy tissues and transforming them to pathological tumor state is a concern. Besides, the emergence of drug resistance, recurrence and adverse eﬀects are the main obstacles widely associated with long duration chemo and radiotherapy of cer-vical cancer, and they further aggravate the burden in patients by means of reducing the quality of life. Preclinical studies in recent years suggest that there is a mounting interest to use bioactive flavonoids as non-toxic therapeutic alternatives to treat chronic pathological condi-tions including cancer . However, translation of their therapeutic
Abbreviations: Ru-Fu, Rutin-Fucoidan; HaCaT, Human keratinocyte cells; HeLa, Epithelial adenocarcinoma cells of the cervix; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; DMEM, Dulbecco's Modified Eagle's Medium; FBS, Fetal bovine serum; LDH, Lactate dehydrogenase; AO, Acridine Orange; EtBr, Ethidium Bromide; DCFH-DA, Dichloro-dihydro-fluorescein diacetate; Rh-123, Rhodamine 123; Δψm, Mitochondrial potential loss; DAPI, 4′,6-diamidino-2-pheny-lindole; FITC, Fluorescein isothiocyanate; PI, Propidium iodide; DMSO, Dimethyl sulfoxide; PBS, Phosphate Buﬀered Saline; MFI, Mean fluorescence intensity; IC, Inhibitory Concentration; ROS, Reactive oxygen species; OD, Optical Density; CI, Combination Index; kDa, kilodalton; A, Absorbance
Corresponding author at: Laboratory of Aquabiotics/Nanoscience, Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, India. E-mail address: [email protected] (R. Thirumurugan).
potential from bench to bed scale is unsuccessful due to their low bioavailability and their extensive biotransformation into less active metabolites in vivo . To overcome these limitations in addition to widening the scope of bioactive therapy, preparing stable bioactive complexes by integrating the distinct functions of individual natural compounds is a feasible alternative to the single compound based therapy [5,6]. Non-covalent interactions between the natural com-pounds in a suitable chemical environment not only facilitate assembly of the compounds together stably but also integrate the structural and functional features of individual compounds . The complex is stable in normal physiological conditions or in blood circulation but dis-sociates in sub cellular compartments when the target cells uptake the complex . The characteristic low pH environment of endosome compartments favours the dissociation of complex and subsequent in-duction of cell death through the individual eﬀects of compounds . This strategy may enhance the therapeutic eﬀect of natural compounds on cellular targets at minimal concentrations of individual compound .
Rutin, a hydrophobic polyphenolic flavonoid phytochemical, has evinced various pharmacological properties . The chemo-preventive activity of rutin has been well demonstrated in vitro and in vivo against several cancers such as leukaemia , colon , neuroblastoma , colorectal , hepatocellular carcinoma , pulmonary metastasis  and breast cancer . However, the poor bioavailability through oral administration and metabolic instability limit the use of rutin in clinical studies . Previous studies suggest that rutin in the form of nanoparticles or complexes exhibits desirable bioavailability with en-hanced chemo-preventive eﬃcacy [4,16].