Therapeutic Effects of Natural Products on Cervical Cancer: Based on Inflammatory Pathways

Abstract

Inflammation is a protective response of the body to an irritant. When an inflammatory response occurs, immune cells are recruited to the injury, eliminating the irritation. The excessive inflammatory response can cause harm to the organism. Inflammation has been found to contribute to cervical cancer if there is a problem with the regulation of inflammatory response. Cervical cancer is one of the most common malignant tumors globally, and the incidence tends to be younger. The harm of cervical cancer cannot be ignored. The standard treatments for cervical cancer include surgery, radiotherapy and chemotherapy. However, the prognosis for this treatment is poor, so it is urgent to find a safer and more effective treatment. Natural products are considered excellent candidates for the treatment of cervical cancer. In this review, we first describe the mechanisms by which inflammation induces cervical cancer. Subsequently, we highlight natural products that can treat cervical cancer through inflammatory pathways. We also introduce natural products for the treatment of cervical cancer in clinical trials. Finally, methods to improve the anticancer properties of natural products were added, and the development status of natural products was discussed.

Keywords: HPV; cervical cancer; inflammatory; natural products; therapeutic.

FIGURE 1

The process by which HPV infected cells becomes cancerous. The process by which HPV infected cells becomes cancerous. HPV virus particles are released when HPV infected cells undergo lysis. At this point, immune cells are recruited by virus particles and release pro-inflammatory cytokines. Inflammation will persists if the virus particles are not completely removed in time. This could cause HPV infected cells to become cancerous.

FIGURE 2

Signaling pathways in the initial stage of cervical cancer cells. NF-κB is activated by pro-inflammatory cytokines such as IL-1β. NF-κB can not only change cytosine into thymine, but also induce CDA expression, thereby inducing gene mutation. The accumulation of inflammatory cells allows ROS to accumulate. The buildup of ROS could cause DNA damage. HPV E6 oncoprotein can inhibit GSH and CAT. ROS is further accumulated.

FIGURE 3

Signaling pathways in the development stage of cervical cancer cells. E7 oncoproteins binds to the PRB-E2F complex, a step that separates E2F from pRb. In the case of high E2F expression, cells will pass the G1/S phase and pRb will eventually be degraded by the proteasome. The STAT3 signaling pathway can be activated by IL-6 to promote cell proliferation which can also be induced by HIF-1α, E5 can inhibit the expression of p21^WAF1, thus promoting the separation of E2F from pRb, and regulate STAT3 by regulating EGFR.