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Published on: July 26, 2017
An Asparagus polysaccharide fraction inhibits MDSCs by inducing apoptosis through toll-like receptor 4
Wensheng Zhang1, Wanzhuo He2, Xiaodong Shi2
1Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, China.
Abstract:
Despite decades of research, malignant tumors are extremely difficult to eliminate with conventional methods. Although surgical resection potentially eradicates the problem, only a few cases are suitable for operation, and other approaches often involve harmful consequences. Revolutionary methods are desperately needed to improve patient outcomes and diminish harmful side effects. Myeloid-derived suppressor cells (MDSCs), downregulators of the innate and adaptive immune systems, have been widely studied over the past 2 decades. MDSCs inhibit the antitumor immune response by suppressing T cell proliferation, cytokine production, and tumor cell killing. With MDSCs becoming novel targets in cancer therapy, our research has focused on the anti-MDSC function of Asparagus polysaccharide (AP), extracted from asparagus, a traditional Chinese herb. In this study, we have used MDSCs isolated from the spleen of mice with colon cancer as an in vitro model to assess the efficacy of AP. Treatment of MDSCs with AP significantly decreased cell proliferation and induced apoptotic cell death through a toll-like receptor 4 dependent way. Subsequent studies showed that the AP treatment enhanced the expression of Bax and Caspase-9 and inhibited the expression of Bcl-2, suggesting that AP induced apoptosis in the MDSCs via the intrinsic pathway. Altogether, the results showed that AP exhibited a significant anti-MDSC activity and attenuated suppression of the antitumor immune response, thereby indicating its potential use in cancer therapy.
Insights
Asparagus polysaccharide (AP) effectively targets myeloid-derived suppressor cells (MDSCs) in colon cancer models. This natural compound reduces MDSC proliferation and induces apoptosis, offering potential for novel cancer therapies by restoring antitumor immunity.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Malignant tumors are challenging to treat with conventional methods, necessitating innovative therapeutic strategies.
- Myeloid-derived suppressor cells (MDSCs) are key inhibitors of antitumor immune responses, making them significant targets in cancer therapy.
- Existing cancer treatments often have severe side effects, highlighting the need for safer, more effective approaches.
Purpose of the Study:
- To investigate the anti-MDSC function of Asparagus polysaccharide (AP), a compound derived from the traditional Chinese herb asparagus.
- To evaluate the efficacy of AP in reducing MDSC proliferation and inducing apoptosis in an in vitro colon cancer model.
Main Methods:
- Isolation of MDSCs from the spleens of mice with colon cancer to establish an in vitro model.
- Treatment of isolated MDSCs with AP to assess its effects on cell proliferation and death.
- Analysis of apoptosis pathways, including toll-like receptor 4 (TLR4) dependency and the intrinsic apoptotic pathway (Bax, Caspase-9, Bcl-2 expression).
Main Results:
- AP treatment significantly decreased the proliferation of MDSCs.
- AP induced apoptotic cell death in MDSCs via a TLR4-dependent mechanism.
- AP modulated the expression of key apoptosis-related proteins (Bax, Caspase-9, Bcl-2), indicating activation of the intrinsic apoptotic pathway.
Conclusions:
- Asparagus polysaccharide (AP) demonstrates significant anti-MDSC activity.
- AP attenuates the immunosuppressive function of MDSCs, potentially restoring antitumor immune responses.
- AP shows promise as a novel therapeutic agent for cancer treatment.
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