Novel Anti-Cancer Products Targeting AMPK: Natural Herbal Medicine against Breast Cancer

Abstract

Breast cancer is a common cancer in women worldwide. The existing clinical treatment strategies have been able to limit the progression of breast cancer and cancer metastasis, but abnormal metabolism, immunosuppression, and multidrug resistance involving multiple regulators remain the major challenges for the treatment of breast cancer. Adenosine 5′-monophosphate (AMP)-Activated Protein Kinase (AMPK) can regulate metabolic reprogramming and reverse the “Warburg effect” via multiple metabolic signaling pathways in breast cancer. Previous studies suggest that the activation of AMPK suppresses the growth and metastasis of breast cancer cells, as well as stimulating the responses of immune cells. However, some other reports claim that the development and poor prognosis of breast cancer are related to the overexpression and aberrant activation of AMPK. Thus, the role of AMPK in the progression of breast cancer is still controversial. In this review, we summarize the current understanding of AMPK, particularly the comprehensive bidirectional functions of AMPK in cancer progression; discuss the pharmacological activators of AMPK and some specific molecules, including the natural products (including berberine, curcumin, (−)-epigallocatechin-3-gallate, ginsenosides, and paclitaxel) that influence the efficacy of these activators in cancer therapy; and elaborate the role of AMPK as a potential therapeutic target for the treatment of breast cancer.

Cytotoxic, Antibacterial, and Antioxidant Activities of the Leaf Extract of Sinningia bullata

“…Plant-derived natural products, whether as pure compounds or standardized extracts, have received attention due to their many health benefits and offer countless prospects for new drug discovery [ 31 , 32 , 33 ]. Natural products possess structural complexity, diversity, and chirality with attractive functions and biological activities that have significantly impacted drug development initiatives [ 34 ].…”

Synthesis, anticancer evaluation and in silico studies of novel N‐substituted arylidenethiazolidine‐2,4‐dione derivatives as adenosine monophosphate‐activated protein kinase activators

“…Initially, commercially available thiazolidine 2,4-dione (1) was reacted with (1-methylcyclohexyl)methanol (2) under standard Mitsunobu reaction condition (DIAD/PPh 3 ) [25] to get N-substituted intermediate (3) [23] which was further treated with commercially available 2-aminothiazole-5-carbaldehyde (4) using catalytical piperidine to prepare corresponding N-substituted arylidenethiazolidine-2,4-dione (5). The coupling of aminothiazole (5) with 4-nitro-3-(trifluoromethyl)benzenesulfonyl chloride (6) was carried out by TEA at room temperature to get targeted hybrid of N-substituted arylidenethiazolidine-2,4-diones with thiazole-benzenesulfonamide (7) in excellent yield (83%).…”

“…Interestingly, PC3 cells were found more susceptible than MDMB-231 cells against these agents. Of these derivatives, thiazolidine 2,4-dione containing indole or azaindole scaffolds (12,13,16,25) found to be more potent than thiazole-thiazolidine 2,4-dione hybrid (7). Particularly, molecular hybridization of thiazolidine 2,4-dione with N-2-(4-(trifluoromethyl)phenyl)ethanol and azaindole (compound 16) was the most effective among the series resulted in potent antiproliferative activity toward both PC3 and MDMB-231 cell lines with IC 50 4.28 μM and 2.5 μM, respectively.…”

“…Recent studies showed that activated AMPK functioned as metabolic tumor suppressor that inhibited both PI3K/Akt pathway as well as the cell cycle regulatory proteins p21, p27, and p53 leading to inhibition of cell proliferation and cell cycle arrest [5,6]. Consequently, a number of natural products, herbal medicines, and synthetic small molecule heterocycles have been reported as AMPK activators against various cancer cell growths [2,7,8]. Thus, AMPK emerged as a druggable target for the treatment of various types of cancers.…”

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

“…In humans, AMPK regulates glucose and fatty acid metabolism through multiple mechanisms 233 . Under normal physiological conditions, activation of the AMPK signaling pathway can promote catabolism, inhibit anabolism, and increase intracellular ATP levels 234 . When AMPK is activated by p53, it can also promote the phosphorylation and acetylation of p53, forming a positive feedback regulatory loop 235,236 .…”