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Mol Immunol. 2017 Jan;81:92-101. doi: 10.1016/j.molimm.2016.10.010. Epub 2016 Dec 1.

Lipopolysaccharides-stimulated macrophage products enhance Withaferin A-induced apoptosis via activation of caspases and inhibition of NF-κB pathway in human cancer cells.

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Department of Pathophysiology, Guangzhou Medical University, Guangzhou, Guangdong 511436, China.
Department of Pathology, School of Basic Medicine, Hubei University of Medicine, Shiyan, Hubei 442000, China.
Department of Pathology, Guangzhou Nansha Central Hospital, Guangzhou First Municipal People's Hospital, Guangzhou, Guangdong 510180, China.
Department of Pathophysiology, Guangzhou Medical University, Guangzhou, Guangdong 511436, China; Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, Guangdong 511436, China. Electronic address:


Macrophages, as a major cellular component in tumor microenvironment, play an important role in tumor progression. However, their roles in modulation of cytotoxic chemotherapy are still not fully understood. Here, we investigated the influence of Lipoplysaccharides (LPS)-stimulated macrophage products (LSMP) on Withaferin A (WA), a natural compound that derived from the medicinal plant Withania somnifera, as an antitumor agent in human breast cancer cells MDA-MB-231 and prostate cancer cells PC-3. Our results revealed that LSMP may enhance WA-induced apoptosis in both cell lines, the underlying mechanisms of which are closely associated with activation of caspase-8, -9 and -3, cleavage of poly ADP-ribose polymerase (PARP), as well as specifically inhibiting the translocation of nuclear factor-κB (NF-κB) and down-regulation of anti-apoptotic proteins X-linked inhibitor of apoptosis protein (XIAP) and inhibitor of apoptosis protein (cIAP1/2). These findings demonstrate that macrophages in tumor microenvironment can modulate tumor responses to chemotoxic agents, providing an effective strategy that targets macrophages to enhance the antitumor efficacy of cytotoxic chemotherapy.


Apoptosis; Macrophage; NF-κB pathway; Withaferin A

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