Antitumor Effects and Mechanism of Novel Emodin Rhamnoside Derivatives against Human Cancer Cells In Vitro

Abstract

A series of novel anthracene L-rhamnopyranosides compounds were designed and synthesized and their anti-proliferative activities on cancer cell lines were investigated. We found that one derivative S-8 (EM-d-Rha) strongly inhibited cell proliferation of a panel of different human cancer cell lines including A549, HepG2, OVCAR-3, HeLa and K562 and SGC-790 cell lines, and displayed IC50 values in low micro-molar ranges, which are ten folds more effective than emodin. In addition, we found EM-d-Rha (3-(2”,3”-Di-O-acetyl-α-L-rhamnopyranosyl-(1→4)-2’,3’-di-O-acetyl-α-L-rhamnopyranosyl)-emodin) substantially induced cellular apoptosis of HepG2 and OVCAR-3 cells in the early growth stage. Furthermore, EM-d-Rha led to the decrease of mitochondrial transmembrane potential, and up-regulated the express of cells apoptosis factors in a concentration- and time-dependent manner. The results indicated the EM-d-Rha may inhibit the growth and proliferation of HepG2 cells through the pathway of apoptosis induction, and the possible molecular mechanism may due to the activation of intrinsic apoptotic signal pathway.

Molecular Docking and ADMET Study of Emodin Derivatives as Anticancer Inhibitors of NAT2, COX2 and TOP1 Enzymes

“…Emodin (D1) has been reported to inhibit the proliferation of many cancer cells which include; Colon cancer [3] [4], breast cancer [5] [6], gall bladder cancer [7] [8], pancreatic cancer [9], lung cancer [10] [11] and human cervical cancer [12]. Poor bioavailability and toxicity in vivo have been documented to limit emodin as cancer chemotherapy [13]. Natural emodin glycoside derivatives have been reported to possess high antitumor activities than emodin [13].…”

“…Poor bioavailability and toxicity in vivo have been documented to limit emodin as cancer chemotherapy [13]. Natural emodin glycoside derivatives have been reported to possess high antitumor activities than emodin [13]. It has been shown that modification of the glycoside by addition of sugar chain at carbon-3 hydroxide (C3-OH) increases solubility and antitumor activity of emodin [14].…”

“…Recently, Xing and co-workers [13], reported a novel derivatives of emodin (Table 1) which strongly inhibited anti-proliferative activities on different human cancer cell lines [13]. Thus, possession of broad anti-proliferative activities makes them become potential anticancer agents [13].…”

“…Thus, possession of broad anti-proliferative activities makes them become potential anticancer agents [13]. Despite of the fact that the anticancer activity of these derivatives on various cancer cells has been reported, their biological targets, molecular mechanisms of action and pharmacokinetic profile remain uncovered.…”

“…Having showed broad anticancer activities on various cancer cells [13], emodin derivatives (Table 1) was therefore investigated in silico to reveal whether NAT2, COX2 and TOP1 enzymes are the molecular targets they exert their action. Furthermore, their pharmacokinetic profiles are predicated to unveil their ADMET properties.…”