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Suppressing the mammalian target of rapamycin (mTOR) pathway has emerged as an attractive method for controlling cancer growth and preventing cancers. Epigallocatechin-3-gallate (EGCG) is a well-known chemopreventive polyphenol, and its effects on AMP-activated protein kinase (AMPK) activation were previously reported. In this study the regulatory mechanisms of EGCG on mTOR and Akt, 2 cancer survival signals, and the interrelationships among mTORC1, Akt, and AMPK were examined. It was found that the suppression of mTORC1 by EGCG requires signals from AMPK, however, the inhibition of Akt with EGCG seems to be AMPK independent. Further, there was no clear indication of Akt as an upstream regulator of mTOR in EGCG treated HT-29 colon cancer cells.

Quercetin has been reported to possess therapeutic effects in the treatment of cancers. In this study, the molecular action of quercetin, with emphasis on its ability to control the intracellular signaling cascades of hypoxia inducible factor-1α (HIF-1α), mammalian target of rapamycin (mTOR), and AMP-activated protein kinase (AMPK), responsible for survival or induction of apoptosis in hypoxic MCF-7 cells, was investigated. The effects of quercetin on apoptosis in relation to its ability to prevent HIF-1α induction were investigated. The involvement of HIF-1α reduction in quercetin-based cancer control was clearly shown in conditions of mTOR inhibition by rapamycin, an mTOR inhibitor. Surprisingly, quercetin induced an AMPK-suppressed state in a CoCl2-induced hypoxic condition. It is speculated that quercetin is capable of inhibiting AMPK to decrease HIF-1α, which is a critical survival factor in hypoxia. A complex control of HIF-1α, mTOR, and AMPK is necessary in inducing apoptosis of MCF-7 breast cancer cells under hypoxia.

In this study, the potential of cherry silver berry (Elaeagnus multiflora) as a cancer preventive agent through regulating inflammatory signals including cyclooxygenase-2 (COX-2) and Akt was examined. Cherry silver berry has reported to exert anti-oxidative, anti-inflammatory, and anti-proliferative effects. The extracts from seed and flesh of cherry silver berry were obtained, and analyzed COX-2 and Akt activities in cherry silver berry extract treated HT-29 colon cancer cells. The results showed that the treatment of seed extracts reduced cell viability at the concentrations above 1,600 mg/mL, effectively reduced COX-2 and p-Akt expression. In addition, the anti-inflammatory effects seemed to be related to cancer cell death. Both of seed and flesh extracts inhibited cell growth and induced apoptosis in HT-29 cells. These results suggest that extracts of cherry silver berry may contribute to suppressing cancer growth through its anti-inflammatory and anti-proliferative effects, and natural products used as oriental medicine have the possibility to control tumor cell growth.

It has been well known that resveratrol inhibits the proliferation of various cancer cells. AMP-activated protein kinase (AMPK), a sensor of cellular energy status, has emerged as a potent target for cancer prevention and/or treatment. It has been found that the activation of AMPK by resveratrol was crucial for the inhibition of HT-29 colon cancer cells. Resveratrol strongly inhibited phosphorylation of Akt. The possibility whether AMPK activation was essential to the inhibition of p-Akt was investigated in resveratrol-treated cancer cells. The inhibitory effect of resveratrol on Akt was not observed when AMPK activities were blocked by the treatment with AMPK siRNA at a relatively lower level of resveratrol. However, the higher concentrations of resveratrol inhibited Akt without the activation of AMPK. Therefore, it was concluded that resveratrol could modulate Akt AMPK-dependently or AMPK-independently. The inhibition of Akt along with the activation of AMPK may contribute to the unraveling anti-cancer mechanism of resveratrol.