**2.5 The anticancer effect of** *Ginkgo Folium* **extract**

The anticancer effect of *Ginkgo Folium* was studied extensively in recent years. The tumor inhibition effect of *Ginkgo Folium* was demonstrated in mouse S180 mouse sarcoma, which might be due to the elevation on free radical scavenger

enzymes [58]. The main reported death way induced by *Ginkgo Folium* is caspase dependent apoptosis that was observed in several cancer types, including cervical cancer [59], colon cancer [60], gastric cancer [61], melanoma [62]. The mechanism responsible for *Ginkgo Folium* induced apoptosis is the disruption on the balance of antiapoptotic protein Bcl-2 and proapoptotic protein BAX, characterized by the decrease on Bcl-2 and the increase on BAX.

Despite of apoptosis, *Ginkgo Folium* can also arrest cell cycle and inhibit cancer cell migration and invasion. The cell cycle arrest induced by *Ginkgo Folium* was due to the suppression on G0/G1 phase in gastric cancer [61, 63]. The suppression on cancer cell migration and invasion were observed in several cancer types through multiple ways. First, upregulation on E-cadherin via lincRNA-p21 mediated suppression on E-cadherin degradation in colon cancer [64]. Second, downregulation on ERK/NF-kB signaling in gastric cancer [65]. Third, inhibition on heat-shock protein 27 (HSP27) mediated by AKT and p38 MAPK pathways in NSCLC [66].

The extracts of *Ginkgo Folium* can combine with herbal formulation to exhibit synergistic effect on anticancer. For instance, it was reported that a new formulation consisted of *Ginkgo Follium* and an herbal mixture Yu Ping Feng San can sensitize cisplatin resistant lung cancer cells through WT1/MVP mediated stabilization on mTOR/AKT pathway [67]. There are few clinical studies on anticancer effect of *Ginkgo.* Considering *Ginkgo Folium* extract has the standard commercial product EGb761, thus, it will be alliable to conduct clinical research with EGb761 to observe whether *Ginkgo* could serve as an adjuvant therapy on anticancer.
