Polyphenols, Luteolin and Pelargonidin, Modulate Radio- and Chemo-Sensitivity on Breast Cancer

Abstract

T HE present study aims at elucidating the role of luteolin (LUT) in modifying the sensitivity of gamma radiation and cisplatin toward breast cancer. Likewise, pelargonidin (PEL) has been tested for its capability to enhance radiosensitivity. Human breast (MCF-7) cancer cell lines were incubated at different doses of LUT and PEL. Cells were exposed to gamma radiation combined with different LUT and PEL doses. The MTT test and calcein staining were used to evaluate the cell viability. For evaluation of LUT biocompatibility with normal mammary tissues, female Wistar rats were divided into three experimental groups (n= 6): control, irradiated (6 Gy), Irradiated (6 Gy) + LUT (dose 30 mg/kg, i.p.). Mammary tissues were collected for further determination of oxidative stress and lactated dehydrogenase (LDH). Either LUT or PEL could increase the sensitivity of gamma radiation applied on MCF-7 cells. In parallel, LUT modified the cisplatin effects on the same cell line. LUT exerted its cytotoxic impact through the GSK-3β-dependent effect, which was elucidated through the combined downregulation effect of GSK-3β inhibitor on MCF-7 cells. Moreover, LUT showed a protective effect on normal mammary tissues in the irradiated rats marked by balanced oxidative status and reduced LDH level. In sum, polyphenols (LUT or PEL) could be used as adjuvant therapeutic agents in the treatment of breast cancer with a further protective effect of normal healthy tissues against cytotoxic therapies.