Induction of Apoptosis in Tumor Cells by Three Naphthoquinone Esters Isolated from Thai Medicinal Plant: Rhinacanthus nasutus KURZ.

Abstract

Cancer causes significant morbidity and mortality and is a major public problem world widely. Cancer chemotherapy, a routine method for the treatment in cancer patients, faces on the problems of unstable efficiency, severe side effects, and cost. Therefore, new drugs with high efficacy without severe side effects, along with understanding the molecular basis in cancer treatment, are awaited.Many attentions have been focused on natural products as potential sources of novel anticancer drugs over the decades. 1)Rhinacanthus nasutus KURZ. (family Acanthaceae), has been used as Thai traditional medicine for the treatment of various cancers, e.g. cervical and liver cancers.2) Various parts of this plant have been also used for the treatment in various other diseases such as eczema, pulmonary tuberculosis, herpes, hepatitis, diabetes, hypertension, and various skin diseases, and the active components of this plant have been widely investigated. [2][3][4][5][6][7][8][9][10][11][12] The main bioactive components of the plant are known to be naphthoquinones such as rhinacanthins (A-D, G-Q), rhinacanthone and lignan groups.3-12) Naphthoquinone compounds have been reported to possess antiproliferative activity against a panel of cancer cells.3,9-12) Recently, our group reported that synthesized compounds of 1,2-naphthoquinones and 1,4-naphthoquinones as well as rhinacanthins-M, -N and -Q, and related naphthoquinone esters showed selective antiproliferative activity against human cancer cells (KB, HeLa and HepG2) with moderate cytotoxicity against non-tumorigenic Vero cells. 13,14) Regarding to the antitumor effects, it was reported that ethanolic and aqueous extracts of the roots and leaves of R. nasutus KURZ. suppressed the growth of ascites sarcoma 180 in Swiss mice, and that rhinacanthin-C was expected as the bioactive compound.11) Moreover, the antitumor activity of rhinacanthone against Dalton's ascites lymphoma was also observed. 12)However, there was no report elucidating the action targets and anticancer mechanism of these potential natural compounds, except one report that both synthesized rhinacanthins-N and -Q could inhibit DNA topoisomerase II, which is known to play a key role in the regulation of cells growth. 14)By the way, it is well recognized that many of available chemotherapeutic drugs including topoisomerase inhibitors mediate their anticancer effects via apoptosis induction in cancer cells.15) Moreover, many drugs derived from natural products such as etoposide, camptothecin, b-lapachone, and so on are known to induce apoptosis. [16][17][18][19][20][21][22][23][24][25][26][27] Especially, b-lapachone, a naturally produced from naphthoquinone compound having similar basic structure to rhinacanthone, showed potent inhibition of DNA topoisomerase I and II, 16,17) and induced apoptosis in various cancer cells. [25][26][27][28][29][30][31] Therefore, it is possible that rhinacanthins would damage tumor cells through the induction of apoptosis. The present study, we investigated the growth inhibitory effect...

Roles of Plant Extracts and Constituents in Cervical Cancer Therapy

“…Rhinacanthins-C, -N and -Q isolated from dried roots of Rhinacanthus nasutus, a plant traditionally used in Thai folk medicine for treating various cancers including cervical and hepatocellular cancers, has been shown to suppressed HeLa cells through induction of apoptosis by activation of caspase-3 pathway (Siripong et al, 2006a). The same group have also shown that when these naphthoquinone esters are liposomalized with egg yolk phosphatidylcholine (EPC) and egg yolk phosphatidylglycerol (EPG), there was significant increase in the antiproliferative effects on HeLa cells as measured by cell proliferation assay (Siripong et al, 2006b).…”

Synthesis and Anticancer Evaluation of Naphthoquinone Esters with 2′-Cyclopentyl and 2′-Cyclohexyl Substituents

“…With respect to the naphthoquinone benzoate esters (7-9 and 13-15), the OH and OMe groups on the benzoate part of 2 0 -cyclopentyl naphthoquinone esters 8 and 9 conferred less activity against all three tested cancer cell lines than the one with no C-1 substitution (7) which corresponds to the analogues of the 2 0 ,2 0 -dimethyl naphthoquinone esters in our previous work. 1) In contrast, an OH group Esters 7,9,10,12,13,15,16,and 18.…”

“…7) Liposomal formulations of rhinacanthins have been studied and showed strong antiproliferative activity against HeLaS3 cells. 8) Moreover, apoptosis induction by rhinacanthones 9) and rhinacanthins 10) has also been investigated.…”

“…We therefore investigated the synthesis of naphthoquinone esters with a 2 0 -cyclopentyl and 2 0 -cyclohexyl substituent on the propyl side chain. Twelve new naphthoquinone esters (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) (Fig. 2) were synthesized and their cytotoxicity evaluated against KB, HeLa, and HepG 2 cancer cell lines.…”

In Vitro Phytochemical and Antibacterial Studies on Rhinacanthus Nasutus (L.) Kurz - A Medicinally Important Plant

“…Several reports of investigation states that leaves and stems of R. nasutus contains various types of flavonoids, benzenoids, coumarin, anthraquinone, quinone, glycosides, carbohydrate, triterpenes, sterols, and chlorophyll [5]. The naphthoquinone; rhinacanthins (A-D, G-Q), rhinacanthone and lignan groups are the main bioactive compounds [6]. The leaf petroleum ether fraction shows significant mosquitocidal activity [7].…”