Induction of Apoptosis by Rhinacanthone Isolated from <i>Rhinacanthus nasutus</i> Roots in Human Cervical Carcinoma Cells

Abstract

Cervical cancer is one of the most commonly diagnosed cancers in woman worldwide and is the first leading cause of cancer-related deaths in Thai women.1) The major cause of mortality associated with this disease is the metastasis of cancer cells that fails to respond to chemotherapeutic drugs. 2)Novel preventive and therapeutic strategies are therefore urgently needed to decrease the mortality associated with this malignancy.Natural products have been found to be a potential source of novel anticancer drugs over the decades and have much contributed to cancer chemotherapy such as etoposide, camptothecin, paclitaxel, etc. 3) In addition, these chemotherapeutic agents have been reported to exert their antitumor effects by inducing apoptosis. 4) Thus, chemical agents with strong apoptosis-inducing activity but minimal toxicity would be expected to have a potential utility as anticancer drugs.Rhinacanthone (3,4-dihydro-3,3-dimethyl-2H-naphthol-[1,2-b]pyran-5,6-dione), one of the main bioactive naphthoquinones, was isolated from Rhinacanthus nasutus which traditionally used in Thai folk medicine for treating various cancers including cervical and hepatocellular cancers. It has also been reported to have antiproliferative activity in various cancer cells 5,6) and antitumor activity against Dalton's lymphoma in mice.7) It has chemical structure closely related to b -lapachone (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione) which was proved to be a novel anticancer drug and DNA topoisomerase I and II inhibitor. 8-11)Recently, we reported that rhinacanthins (C, N and Q), another naphthoquinones isolated from the Rhinacanthus plant, exhibited antiproliferative activity in various cancer cells 5) and induced apoptosis in human cervical carcinoma (HeLaS3) cells involving in G 2 /M cell cycle arrest and activation of caspase-3. 12) Rhinacanthins-N and -Q also act as topoisomerase II inhibitors.13) Therefore, it is possible that rhinacanthone functions on cancer cells by the same action as b-lapachone and/or rhinacanthins. Up to present, the potential anticancer mechanism(s) of this drug has not been elucidated. In present study, effects of rhinacanthone on the induction of apoptosis and its molecular mechanism in human cervical carcinoma (HeLa) cells were investigated. Here, we demonstrate that rhinacanthone, 1,2-naphthoquinone, induces apoptosis on human cervical carcinoma cells. To the best of our knowledge, this is the first report showing that rhinacanthone-induced apoptotic cell death is mediated via mitochondria-dependent pathway. Rhinacanthone would be a candidate for apoptosis-inducing cancer Rhinacanthone, a main bioactive naphthoquinone, isolated from roots of Rhinacanthus nasutus KURZ, (family Acanthaceae), a Thai traditional medicine, has been reported to possess anticancer effects, although the anticancer mechanism is still unclear. Therefore, we investigated the effects of rhinacanthone on cell proliferation, cell cycle progression and apoptosis induction in human cervical carcinoma ( The apoptot...

Roles of Plant Extracts and Constituents in Cervical Cancer Therapy

“…This is not surprising since another alkaloid-taxol, derived from plant have been routinely used as an anticancer drug under different brand names worldwide. However, another compoundrhinacanthone isolated from R. nasutus has also exhibited cytotoxicity to cervical cancer cells at a very low concentration (Siripong et al, 2009). Rhinacanthone role becomes quite significant since it is known to induce apoptotic cell death through multiple pathways as mentioned previously.…”

“…In another work involving rhinacanthone (3,4-dihydro-3,3-dimethyl-2H-naphthol-[1,2-b]pyran-5,6-dione), one of the main bioactive naphthoquinones, isolated from Rhinacanthus nasutus possess cytotoxic activity in HeLa cells as indicated by MTT assay (Siripong et al, 2009). Treatment of cell culture with rhinacanthone resulted in a significant decrease in cell proliferation in a dosedependent manner.…”

“…Others such as the extracts of A. confertifolia, has indicated the significant toxic effects in cervical cancer cells in a concentration comparable to those of the FDAapproved anti-cancer drug drug Onxol ® especially at the highest doses (Capua et al, 2010). Rhinacanthone, bioactive compound isolated from R. nasutus, has been shown to possess greater efficacy than β-lapachone, an anticancer drug under similar conditions (Siripong et al, 2009).…”

Anti-metastatic Effects on B16F10 Melanoma Cells of Extracts and Two Prenylated Xanthones Isolated from Maclura amboinensis Bl. Roots

“…Cell cycle phase distribution was analyzed by flow cytometry with propidium iodide (PI) staining, as described previously (Siripong et al, & 2009. In brief, B16F10 melanoma cells (1x10 6 cells/dish) were seeded on 60 mm dishes (Corning Incorporation, MA, USA) and incubated at 37°C, 5% CO 2 for 24 h. Cells were then treated with four extracts; n-hexane, chloroform, methanol (3, 10 and 30 µg/ml) and aqueous extract (250, 500 and 750 µg/ ml) as well as two main xanthones; MA-1 and MA-2 (3, 10 and 20 µM) for 24 h. Doxorubicin (1, 3 and 10 µM) and 0.1% DMSO in medium were used as positive and negative controls.…”

“…All experiments were performed in duplicate DOI:http://dx.doi.org/10.7314/APJCP.2012.13.7.3519 Anti-metastatic Effects of Maclura amboinensis Bl. on B16F10 Melanoma Cells and reproducibility was checked in three independent experiments (Siripong et al, : 2009.…”