Atractylenolide III induces apoptosis by regulating the Bax/Bcl-2 signaling pathway in human colorectal cancer HCT-116 Cells in vitro and in vivo

Abstract

Atractylodes is the dry root of atractylodes macrocephala koidz and has been commonly used as a traditional Chinese medicine (TCM). Atractylenolide III, a main component of atractylodes, has displayed significant effects on anti-inflammation and anticancer. However, the effects of atractylenolide III on growth inhibition and apoptosis induction in colon cancer remain unclear. The results showed that atractylenolide III significantly inhibited the cell growth and induce cellular apoptosis in HCT-116 cells in a concentration dependence manner in vitro. Mechanistic studies further showed that atractylenolide III could regulate the Bax/Bcl-2 apoptotic signaling pathway through promoting the expression of proapoptotic related gene/proteins Bax, caspase-9 and caspase-3 but inhibiting the expression of antiapoptotic related gene/protein Bcl-2 in HCT-116 cells. Furthermore, atractylenolide III also significantly inhibited the tumor growth of HCT-116 tumor xenografts bearing in nude mice through inducing apoptosis by upregulation of the expressions of Bax, cleaved caspase-3 and p53 but downregulation of the expressions of Bcl-2 in tumor tissues in vivo. The studies may provide the scientific rationale for the understanding of the anticancer effect of atractylenolide III. Therefore, atractylenolide III may have the potential to be developed as a promising novel anticancer agent for the treatment of colorectal cancer clinically.

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“… 59 , 60 Therefore, we chose iNOS, Arg-1 and CD206 as indicators to detect macrophage polarization. Meanwhile, since BAX and Bcl2 are key factors in the process of apoptosis, 61 the correlation and ratio of the two determine the survival or death of cells after apoptotic stimulation. 62 Most of the studies have used the examination of BAX and BCL2 expression levels to verify apoptosis.…”

“…62 Most of the studies have used the examination of BAX and BCL2 expression levels to verify apoptosis. [61][62][63][64] Therefore, we likewise chose BAX and Bcl-2 as indicators to detect apoptosis. We found that human monocyte-derived macrophages co-cultured with KCs-oe-MALAT1-Exo possessed greater cytophagocytosis, weaker apoptosis and a greater tendency to polarize towards the M2 phenotype.…”

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“…Grayscale analysis of the western blot images was conducted with Photoshop (Microsoft Corporation). 30…”

The function of natural compounds in important anticancer mechanisms

“…Hinesol, a compound extracted from Atractylodes Rhizoma application in the study of non-small cell lung cancer, induces proliferation, inhibition, and apoptosis in non-small cell lung cancer cell lines by up-regulating Bax and inhibiting the expression of Bcl-2 ( 40 ). Atractylenolide III is a kind of anti-inflammatory and anti-tumor active substance, that induces apoptosis of human colon cancer HCT-116 cells by promoting apoptosis-related genes, regulating the Bax/Bcl-2 apoptosis signaling pathway, and the expression of caspase-3 and p53 ( 41 ).…”