Aged black garlic extract inhibits the growth of estrogen receptor-positive breast cancer cells by downregulating MCL-1 expression through the ROS-JNK pathway

Abstract

The black garlic is produced from the raw garlic by Milliard reaction at high temperature (~60–90°C) and humidity (~70–90%). In this process, the pungent odor and gastrointestinal irritation effects of the raw garlic are reduced. At the same time, unstable compounds such as allicin are converted into stable organosulfur compounds with antioxidant activity. Previous studies have confirmed that black garlic extract has anti-tumor effects and could inhibit the proliferation of various tumor cells, including breast cancer cells MCF-7. However, the mechanisms of the anti-tumor effects remain unclear. In this study, we found that the black garlic extract could inhibit the proliferation, invasion, and metastasis of estrogen receptor-positive breast cancer cells, promote their apoptosis, and inhibit their epithelial-mesenchymal transition. Mechanistically, the black garlic extract reduced the expression of the anti-apoptotic protein MCL-1, which was achieved by modulating the ROS-JNK signaling pathway. In addition, the black garlic extract also decreased the expression of BCL-2 and increased the expression of BAX and BIM. We also found that the black garlic extract, in combination with venetoclax, a BCL-2 inhibitor, synergistically kills the estrogen receptor-positive breast cancer cells. These results suggested that black garlic extract has great therapeutic value and prospects for estrogen receptor-positive breast cancer treatment.

S-Allyl-L-Cysteine Affects Cell Proliferation and Expression of H2S-Synthetizing Enzymes in MCF-7 and MDA-MB-231 Adenocarcinoma Cell Lines

“…The described effect and antitumor potential of SAC is unique for cancer cell models. Yang et al [60] studied the effects of ABGE, the water-soluble components of mature black garlic extract that is S-allyl cysteine (SAC) and S-allyl mercaptocysteine (SMAC). In the normal mammary cell line MCF-10A, they observed that ABGE had no inhibitory effect on the growth of the cells.…”

Anti-Cancer and Anti-Inflammatory Properties of Black Garlic

“…On the other hand, no anti-proliferative and pro-apoptotic effects were demonstrated in the MCF-10A breast cancer cell line [16]. In a study on three lung cancer cell lines (H1975, H520, A549), water and alcohol extracts also showed negligible anti-proliferative properties [46].…”

“…It has been shown that mature black garlic extract inhibits the proliferation, migration, invasion, and metastasis of ER+ breast cancer cells in the MCF-7 and MDA-MB-361 cell lines [16]. Moreover, it stimulates apoptosis in ER+ breast cancer cells via the inhibition of the expression of anti-apoptotic proteins MCL-1 and BCL-2, while stimulating the expression of pro-apoptotic proteins BIM and BAK [16]. The reduction in MCL-1 expression was mediated by JNK activation caused by an increase in the amount of reactive oxygen species in cancer cells [16].…”

“…Moreover, it stimulates apoptosis in ER+ breast cancer cells via the inhibition of the expression of anti-apoptotic proteins MCL-1 and BCL-2, while stimulating the expression of pro-apoptotic proteins BIM and BAK [16]. The reduction in MCL-1 expression was mediated by JNK activation caused by an increase in the amount of reactive oxygen species in cancer cells [16].…”

“…As it ages under precisely defined processing parameters, e.g., temperature or humidity, the color of garlic changes from white to dark brown/black [15]. The color change is the result of enzymatic browning in the Millard reaction-condensation between the reducing carbonyl group of sugar and the amino group [10,[15][16][17]. In Figure 2, we can visualize the difference between fresh garlic and aged garlic.…”