Growth inhibition and apoptosis-inducing effect on human cancer cells by RCE-4, a spirostanol saponin derivative from natural medicines

Abstract

Reineckia carnea has been used to treat several diseases in folk remedies. RCE-4 has been isolated from several plants of the family Liliaceae, but its biological activity has not yet been reported. In the present study, we found that RCE-4 exhibited potent cytotoxicity to the tested human cancer cell lines, and the CaSki cell line was the most sensitive with an IC50 of 3.37 µM. Thus, we presented the apoptosis-inducing effect of RCE-4 on CaSki cervical cancer cells and investigated the relevant mechanisms. Based on observations using transmission electron microscopy, RCE-4-treated cells manifested nuclear shrinkage, condensation and fragmentation. Annexin V/PI dual staining flow cytometry assay further confirmed that RCE-4 caused a dose-dependent early apoptotic effect. Prior to these events, RCE-4 triggered a rapid decrease of the mitochondrial membrane potential and caused the release of cytochrome c from the mitochondria into the cytoplasm. RCE-4 increased the expression of Bax and decreased the expression of Bcl-2, thus augmenting the Bax/Bcl-2 ratio. These findings suggest that RCE-4 induces mitochondrial-mediated apoptosis in CaSki cells and has the potential to be developed as an anticancer agent.

Evaluation of uttroside B, a saponin from Solanum nigrum Linn, as a promising chemotherapeutic agent against hepatocellular carcinoma

“…Steroidal glycosides and triterpenes, commonly known as saponins are a group of compounds abundant in plants and have been reported to be cytotoxic to cancer cells of different origins141516. Degalactotigonin, uttroside A and uttroside B are the cytotoxic saponins isolated from S. nigrum Linn89, which is a widely used herb in the Indian traditional systems of medicine.…”

Roles of Plant Extracts and Constituents in Cervical Cancer Therapy

“…RCE-4 isolated from Reineckia carnea has been found to exhibit potent cytotoxicity on yet another cervical cancer cells CaSki (Wang et al, 2013). In this investigation, the IC 50 was found to be 3.37 µM.…”

“…The other cervical cancer cell lines where plant extracts or its derivatives have been found effective are KB3-1 (Staerk et al, 2002;Kaewpiboon et al, 2012), SiHa Gupta eta al., 2013), C33a (Lee et al, 2012) and CaSki (Wang et al, 2013).…”

RCE‑4, a potential anti‑cervical cancer drug isolated from Reineckia carnea, induces autophagy via the dual blockade of PI3K and ERK pathways in cervical cancer CaSki cells

“…In previous studies, RCE-4, as a potential anti-cervical cancer chemotherapy drug, was demonstrated to induce mitochondria-mediated apoptosis, which was considered to be the mechanism for inhibiting the proliferation of CaSki and HeLa cells (5,9). The aim of the present study was to clarify whether RCE-4-induced autophagy is a survival or death mechanism during cervical cancer treatment.…”

“…To the best of our knowledge, the steroidal saponins primarily exert anti-inflammatory and antitumor activity, with toxicity towards both normal and tumor cells (7). However, RCE-4 exhibited a significant anti-inflammatory (8) and notable cytotoxic effects on cancer CaSki, HeLa, HT-29 and CNE-2 cell lines, whereas it exerted relatively weak cytotoxic effects in normal Marc-145 and MDCK cells (9). Furthermore, CaSki cell xenograft experiments using nude mice demonstrated that RCE-4 inhibited tumor growth and had notably low levels of toxicity in normal tissues, including those of the liver and the uterus (10).…”