Rhinacanthus nasutus KURZ. (family Acanthaceae), has been used in Thai traditional medicine for the treatment of various diseases such as eczema, pulmonary tuberculosis, herpes, hepatitis, diabetes, hypertension and various skin diseases, and its active components were widely investigated. 1-7)R. nasutus KURZ. has also been used for cancer treatment. [8][9][10] The main bioactive compounds were revealed to be naphthoquinone; rhinacanthins (A-D, G-Q), rhinacanthone and lignan groups. [1][2][3][4][5][6][7][8]10,11) Antitumor activity of R. nasutus KURZ. extracts,8) and that of rhinacanthone in the in vivo study were reported. 11) We previously reported that rhinacanthins-M, -N and -Q and related naphthoquinone esters as well as synthetic compounds, 1,2-naphthoquinones and 1,4-naphthoquinones, selectively suppressed the growth of KB, HeLa and HepG2 human cancer cells, and normal Vero cells. 12,13) We also performed mechanistic study and observed that synthetic rhinacanthins-N and -Q inhibited DNA topoisomerase II.13) A naphthoquinone compound b-lapachone, that was also derived from natural products and has a similar structure to rhinacanthone, was reported to be a potent inhibitor of DNA topoisomerase I and II, [14][15][16] and to induce apoptosis of various cancer cells. [17][18][19][20][21] Recently, we observed that rhinacanthins-C, -N and -Q suppressed human cervical carcinoma HeLaS3 cells through induction of apoptosis. 22)Therefore, in the present study, we attempted to determine actual antitumor activity of rhinacanthins in tumor-bearing mice.Since rhinacanthins-C, -N and -Q are hydrophobic compounds, they are not able to inject into bloodstream without solubilization. For in vivo use of the drugs, we attempted to solubilize them in liposomes. By the way, liposomes have been widely used in the field of drugs delivery systems (DDS): Liposomalization reduces side effects and toxicities of drugs encapsulated, and improves their bioavailability. Therefore, liposomes tended to be used for cancer treatment, since most of anticancer drugs accompany severe side effects. [23][24][25] Furthermore, liposomes with long circulating characteristics are known to accumulate in interstitial spaces of tumor tissues of which blood vessels are highly permeable. 26,27) For the purpose of DDS, liposomes having rather rigid lipid bilayer are favorable, and they are usually composed of phospholipids with saturated fatty acyl chains and cholesterol. On the other hand, liposomes have been used for the injection of hydrophobic drugs, since hydrophobic materials can be encapsulated into the lipid bilayer of the liposomes. For example, Visudyne, a liposomal formulation of benzoporphyrin derivative monoacid ring A (BPD-MA), is being used clinically in photodynamic therapy for age-related macular degeneration. In Visudyne, liposomes are used as a "solvent" of BPD-MA for the purpose of injection of the drug into bloodstream.28) In such case, liposomes having rather fluid lipid bilayer are used, and the injected drug in the bloodstream is t...

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...

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...

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Thirteen cardenolide glycosides (1-13) were isolated from the CHCl and MeOH extracts of Vallaris glabra leaves. The structures of the new compounds (2-13) were identified by spectroscopic methods, with the absolute configurations of the sugar moieties determined by acid hydrolysis. All compounds were evaluated for their cytotoxic activity against human cervix adenocarcinoma, lung carcinoma, and colorectal adenocarcinoma cell lines. The two most potent compounds [2'-O-acetylacoschimperoside P (1) and oleandrigenin-3-O-α-l-2'-O-acetylvallaropyranoside (2)] exhibited IC values in the range of 0.03-0.07 μM.