The Role of Andrographis paniculata in Modulating the Immune Response in Cancer-Associated Chronic Inflammation, Angiogenesis, and Metastasis
Rengganis Ulvia
1, Andayana Puspitasari Gani
2,3, Retno Murwanti
3,4* 
1 Faculty of Pharmacy, Universitas Gadjah Mada, Jl. Sekip Utara, Sleman, Yogyakarta 55281, Indonesia.
2 Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Gadjah Mada, Jl. Sekip Utara, Sleman, Yogyakarta 55281, Indonesia.
3 Medical Plants and Natural Products Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Sleman, Yogyakarta 55281, Indonesia.
4 Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Jl. Sekip Utara, Sleman, Yogyakarta 55281, Indonesia.
Abstract
The immune system plays an essential role in cancer pathogenesis through providing an inflammatory immune response. Chronic inflammation causes tumor growth, angiogenesis, and metastasis facilitated by interactions between tumor, immune, and stromal cells in the tumor microenvironment (TME). Various inflammatory mediators and growth factors secreted by cells in the TME exert a synergistic effect on cancer promotion. Thus, the development of cancer therapies that lead to inhibition of the activity of immune cells, cytokines, chemokines, and cancer-inducing growth factors is a promising therapeutic strategy. Andrographis paniculata (A. paniculata) is an ethnomedicinal plant with immunomodulatory and anticancer activity. A. paniculata can also inhibit the resistance of chemotherapy agents associated with TME as adjuvant chemotherapy. This review focuses on the mechanism of A. paniculata in suppressing cancer-associated chronic inflammation, angiogenesis, and metastasis through modulation of the immune response. The results show that A. paniculata exerts anticancer effects directly targeting cancer cells, inhibiting cancer growth by modulating immune responses. A. paniculata exerts anticancer effects by inhibiting the production of cytokines, growth factors, and chemokines via the nuclear factor-kappa B (NF-ĸB), mitogen-activated protein kinase (MAPK), Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways. In addition, this review provides a new hypothesis regarding the potential of A. paniculata to serve as an anticancer agent that can inhibit cancer cell proliferation at the angiogenesis and metastatic stages through regulating inflammation due to interactions between cancer cells, immune cells, and stromal cells in the TME.