Barbigerone, a Natural Isoflavone, Induces Apoptosis in Murine Lung-Cancer Cells via the Mitochondrial Apoptotic Pathway

Abstract

Barbigerone is a naturally occurring isoflavone with antioxidant activity. In present study, we investigated the antitumor activity of barbigerone against murine lung cancer cells LL/2 and the possible mechanism in vitro. Our results showed that barbigerone inhibited LL/2 cells proliferation in a concentration- and time-dependent manner and caused apoptotic death of LL/2 cells. Barbigerone-induced apoptosis was characterized by enhanced mitochondrial cytochrome c release, activation of caspase-3,-9, but not caspase-8. Exposure of LL/2 cells to barbigerone resulted in upregulation of Bcl-2-associated protein (Bax) and down-regulation of Bcl-2. In addition, proliferation inhibitory effect of barbigerone was associated with decreased level of phosphorylated p42/44 mitogen-activated protein kinase (p42/44 MAPK) and phosphorylated Akt. Moreover, barbigerone exhibit less toxicity to non-cancer cells than tumor cells. In conclusion, our results indicated that barbigerone can inhibit murine lung cancer cell proliferation by inducing apoptosis via mitochondrial apoptotic pathway and by decreasing phosphorylated p42/44 MAPK and Akt. Its potential to be a candidate of anti-cancer agent is worth being further investigated.

A Novel Benzothiazole Derivative YLT322 Induces Apoptosis via the Mitochondrial Apoptosis Pathway In Vitro with Anti-Tumor Activity in Solid Malignancies

“…The anti-apoptotic Bcl-2 family members such as Bcl-2 and Bcl-xl inhibit cytochrome c release by blocking the activation of pro-apoptotic proteins. For most cancers, the over-expression of Bcl-2 protein associates with poor survival, uncontrolled progression and resistance to anticancer agents, making Bcl-2 family members promising anticancer drug targets [24], [33]–[34]. Our results showed that the expression of Bcl-2 decreased in cells treated with YLT322, whereas that of Bax increased.…”

“…Thus restoring apoptosis is a promising strategy for effectively treating cancers [20]. Currently, many therapeutic approaches, including various biologicals, hormones, and small molecule chemotherapeutic agents such as ABT737, AT101, HS-113 and chloroquine, inhibit tumors by triggering cell apoptosis [18], [21]–[24]. Previous studies have demonstrated that some benzothiazole derivatives can induce apoptosis [10], [13], but the mechanism has not been clearly determined.…”

Barbigerone reverses multidrug resistance in breast MCF‐7/ADR cells

“…Barbigerone (BA) was a naturally occurring isoflavone. Our previous study has shown that BA exhibited antitumor activity on cancer cells by inducing apoptosis (Z. G. Li et al, ). BA could also inhibit angiogenesis and suppress tumor growth through tumor angiogenesis (X. Li, Wang, Ye, Peng, & Chen, ).…”

Barbigerone-in-hydroxypropyl-β-cyclodextrin-liposomal nanoparticle: preparation, characterization and anti-cancer activities

“…Previous reports have demonstrated that Bar exhibits a variety of biological activities, such as antioxidant activity, 15-lipoxygenase inhibitory activity [2] and anti-plasmodial activity against the malarial parasite Plasmodium falciparum [3]. Recent studies by our group have shown that Bar exhibits an anti-cancer potential as it causes apoptosis of murine lung-cancer cells [4]. Bar could inhibit tumorangiogenesis, tumor growth and lung metastasis via downregulation of the MEK3/6/p38 MAPK signaling pathway [5].…”