Crocetin shifts autophagic cell survival to death of breast cancer cells in chemotherapy

Abstract

The chemotherapy with fluorouracil is not always effective, in which some breast cancer cells may survive the fluorouracil treatment through enhanced autophagy. Crocetin is the major constituent of saffron, a Chinese traditional herb, which has recently found to have multiple pharmacological effects, including anticancer. However, the effects of Crocetin on the outcome of fluorouracil therapy for breast cancer have not been studied. Here, we showed that fluorouracil treatment inhibited the growth of breast cancer cells, in either a Cell Counting Kit-8 assay or an MTT assay. Inhibition of autophagy further suppressed breast cancer cell growth, suggesting that the breast cancer cells increased autophagic cell survival during fluorouracil treatment. However, Crocetin significantly increased the suppressive effects of fluorouracil on breast cancer cell growth, without affecting either cell apoptosis or autophagy. Inhibition of autophagy at the presence of Crocetin partially abolished the suppressive effects on breast cancer cell growth, suggesting that Crocetin may increase autophagic cell death in fluorouracil-treated breast cancer cells. Furthermore, Crocetin decreased Beclin-1 levels but increased ATG1 levels in fluorouracil-treated breast cancer cells. Together, these data suggest that Crocetin may shift autophagic cell survival to autophagic cell death in fluorouracil-treated breast cancer cells, possibly through modulation of the expression of ATG1 and Beclin-1.

The Novel Role of Crocus sativus L. in Enhancing Skin Flap Survival by Affecting Apoptosis Independent of mTOR: A Data-Virtualized Study

“…We aimed to study the possible involvement of the mTOR pathway in the protective effects of Saffron. Studies have been performed on the effect of Crocin in liver cancer [ 58 ] and Crocetin in breast cancer [ 59 ] and their effects on autophagy have been reported, but the results of our study showed that Saffron has no effect on mTOR or p-mTOR expression in skin flap tissue. We did not observe significant mTOR and p-mTOR changes between groups.…”

Beclin1 inhibition enhances paclitaxel‑mediated cytotoxicity in breast cancer in�vitro and in�vivo

“…Rai et al (48) demonstrated that resveratrol was able to chemosensitize doxorubicin in combination through suppressing Beclin1 in breast cancer cells. Zhang and Li (49) reported that crocetin may increase autophagic cell death via the inhibition of the expression of Beclin1 in breast cancer cells during fluorouracil treatment. However, few reports have demonstrated an association between Beclin1 and paclitaxel treatment in breast cancer cells.…”

The Natural Carotenoid Crocetin and the Synthetic Tellurium Compound AS101 Protect the Ovary against Cyclophosphamide by Modulating SIRT1 and Mitochondrial Markers

“…It is well established that the therapeutic effects of crocetin against some types of cancers, including breast cancer, have been pointed out [ 47 , 48 , 54 – 56 , 66 – 69 ]. Crocetin acts in a dose-dependent manner in in vitro models [ 47 , 55 , 67 , 68 ]. Oral administration of crocetin has been employed in research on mice aimed to investigate its effects against retinal damage [ 70 ] and tumour growth [ 56 , 69 ].…”