Reactive oxygen species and senescence modulatory effects of rice bran extract on 4T1 and NIH-3T3 cells co-treatment with doxorubicin

Abstract

Objective: To determine the effect of rice bran extract (RBE) in combination with doxorubicin on 4T1 triple-negative breast cancer cells and NIH-3T3 cells. Methods: RBE was obtained by maceration with n-hexane. The phytochemical profile of RBE was observed using highperformance liquid chromatography. Cytotoxic effect of RBE was evaluated through MTT assay. In addition, flow cytometry was used for cell cycle and apoptosis analysis. Cellular senescence was observed using SA-β-Gal assay and intracellular reactive oxygen species (ROS) levels were evaluated using DCFDA staining. The pro-oxidant property of RBE was also evaluated through 1-chloro- 2,4-dinitrobenzene spectrophotometry and molecular docking. Results: RBE was obtained with a yield of 18.42% w/w and contained tocotrienols as the major compound. RBE exerted no cytotoxic effect on 4T1 and NIH-3T3 cells. However, RBE in combination with doxorubicin decreased 4T1 cell viability synergistically (combination index<0.9) and induced apoptosis and senescence on 4T1 cells. RBE significantly decreased senescence in doxorubicin-treated NIH-3T3 cells. Additionally, RBE did not increase ROS levels in doxorubicin-treated 4T1 cells. Meanwhile, the combination of RBE and doxorubicin reduced ROS levels in NIH-3T3 cells. RBE significantly reduced glutathione-S-transferase activity and alpha-tocotrienol interacted with glutathione-S- transferase in the glutathione binding site. Conclusions: Rice bran may be used as a co-chemotherapeutic agent to improve the therapeutic effectiveness of doxorubicin while protecting against the cellular senescence effects of doxorubicin on healthy cells.

Hesperitin Synergistically Promotes the Senescence Induction of Pentagamavunone-1 in Luminal Breast Cancer Cells, T47D

“…In this study, HST demonstrated its ability to increase the efficacy of PGV-1 and could help to protect surrounding cells from damage. In general, cell damage can be induced by oxidative agents including drugs, cellular stress, and poisons (Madkour 2020;Zulfin et al 2021). These findings provide backing for the prospective development of HST as a co-chemotherapeutic agent, capable of enhancing the cytotoxic impact of chemotherapy agents and to reduce the cellular damages caused by toxic agents, including oxidative stress.…”

Cardamom Essential Oil Extract Suppress the Progression of Triple-Negative Breast Cancer 4T1 Cell Line

“…( 16) Senescence is a cellular event occurring naturally as a sign of abnormal ROS level of the cell, leading to apoptosis of the cell. (17,18) This can be one approach for killing cancer cells, including TNBC. On the other hand, it has been mentioned before that TNBC has the lowest prognosis among the different subtypes of cancer.…”