Andrographolide Inhibits Osteopontin Expression and Breast Tumor Growth Through Down Regulation of PI3 Kinase/Akt Signaling Pathway

Abstract

Breast cancer is one of the most common cancers among women in India and around the world. Despite recent advancement in the treatment of breast cancer, the results of chemotherapy to date remain unsatisfactory, prompting a need to identify natural agents that could target cancer efficiently with least side effects. Andrographolide (Andro) is one such molecule which has been shown to possess inhibitory effect on cancer cell growth. In this study, Andro, a natural diterpenoid lactone isolated from Andrographis paniculata has been shown to inhibit breast cancer cell proliferation, migration and arrest cell cycle at G2/M phase and induces apoptosis through caspase independent pathway. Our experimental evidences suggest that Andro attenuates endothelial cell motility and tumor-endothelial cell interaction. Moreover, Andro suppresses breast tumor growth in orthotopic NOD/SCID mice model. The anti-tumor activity of Andro in both in vitro and in vivo model was correlated with down regulation of PI3 kinase/Akt activation and inhibition of pro-angiogenic molecules such as OPN and VEGF expressions. Collectively, these results demonstrate that Andro may act as an effective anti-tumor and anti-angiogenic agent for the treatment of breast cancer.

A map describing the association between effective components of traditional Chinese medicine and signaling pathways in cancer cells in vitro and in vivo

“…The combination of androgarpholide and taxifolin inhibit proliferation and trigger apoptosis of breast cancer cells by disrupting microtubule dynamics and acitivating the spindle assembly checkpoint (SAC) (21). In other studies, androgarpholide alone can inhibit proliferation of breast cancer cells and non-small cell lung cancer (NSCLC) cells by downregulating the PI3K/Akt pathway (22,23). NSCLC cells also can be suppressed by androgarpholide through the HIF-1α pathway (24).…”

Notch1-MAPK Signaling Axis is Essential in CD133+ Melanoma Initiating Cells

“…Moreover, these agents exhibit several side effects and drug resistance [8,17,18]. Studies showed that Andrographolide (Andro), which is derived from Andrographis paniculata, act as an anticancer agent with less side effect and is able to target CSCs in multiple myeloma [19][20][21]. Our data demonstrate that Andro is able to eliminate CD133 + cells from melanoma and reduces the tumor growth.…”

Andrographolide Induces Autophagic Cell Death and Inhibits Invasion and Metastasis of Human Osteosarcoma Cells in An Autophagy-Dependent Manner

“…AG has been reported to possess antitumor activity in various human cancer cell lines, including lung [40], hepatocellular carcinoma [41], breast [42], and colon [43] cancer cells. In this study, we investigated the antitumor effect of AG on human OS cells for the first time and showed that treatment with AG induces autophagy, but not apoptosis, in human OS cells.…”