Abstract
Alisol B 23-acetate (AB23A), a natural triterpenoid from the rhizome of Alisma orientale, a Chinese medicinal herb, has multiple physiological activities including anticancer. However, its effect on human colon cancer and the underlying mechanism are not clear. Here, we reported for the first time that AB23A induced cell cycle G1 phase arrest and apoptotic cell death in colon cancer cells. Autophagy also occurred in AB23A-treated HCT116 cells as evidenced by the accumulation of microtubule-associated protein 1 light chain 3 form II (LC3-II) and degradation of SQSTM1/p62. An autophagy inhibitor, 3-methyladenine (3-MA) was found to attenuate AB23A-mediated autophagy, apoptosis, and cell death, indicating that AB23A-induced apoptotic response was dependent on the induction of autophagy. In addition, the treatment of HCT116 cells with AB23A resulted in the generation of reactive oxygen species (ROS) and phosphorylation of c-Jun N-terminal kinase (JNK). A ROS scavenger, N-acetylcysteine (NAC) and a JNK-specific inhibitor, SP600125 attenuated AB23A-induced autophagy and apoptotic cell death. Moreover, NAC was able to eliminate AB23A-induced JNK phosphorylation. This finding provides a novel mechanism of action of AB23A in colon cancer HCT116 cells that AB23A induces autophagic-dependent apoptotic cell death in colon cancer cells, at least in part, though the accumulation of intracellular ROS and subsequent activation of JNK.
Highlights
Natural products are important sources of novel anticancer agents and contribute a lot to cancer chemotherapy and chemoprevention [1]
Autophagy occurred in Alisol B 23-acetate (AB23A)-treated HCT116 cells as evidenced by the accumulation of microtubuleassociated protein 1 light chain 3 form II (LC3-II) and degradation of SQSTM1/p62
Autophagy serves as a cell survival pathway suppressing apoptosis, and in others, it can lead to cancer cell death both in cells that are capable of apoptotic cell death and in cells that are deficient in apoptotic cell death [11]
Summary
Natural products are important sources of novel anticancer agents and contribute a lot to cancer chemotherapy and chemoprevention [1]. As the type-I programmed cell death (PCD), is a mechanism exploited by many anticancer drugs to cause cancer cell death. A lysosomal catabolic pathway of selfdegradation and recycling of cellular macromolecules and organelles, is often involved in the response to the treatment with anticancer agents [9, 10]. Autophagy serves as a cell survival pathway suppressing apoptosis, and in others, it can lead to cancer cell death both in cells that are capable of apoptotic cell death and in cells that are deficient in apoptotic cell death [11]. Whether AB23A can induce apoptosis or autophagy in AB23A-treated colon cancer cells remains to be determined
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