An immunomodulatory polysaccharide-rich substance from the fruit juice of Morinda citrifolia (noni) with antitumour activity.

The fruit juice of Morinda citrifolia (noni) contains a polysaccharide-rich substance (noni-ppt) with antitumour activity in the Lewis lung (LLC) peritoneal carcinomatosis model. Therapeutic administration of noni-ppt significantly enhanced the duration of survival of inbred syngeneic LLC tumour bearing mice. It did not exert significant cytotoxic effects in an adapted culture of LLC cells, LLC1, but could activate peritoneal exudate cells (PEC) to impart profound toxicity when co-cultured with the tumour cells. This suggested the possibility that noni-ppt may suppress tumour growth through activation of the host immune system. Concomitant treatment with the immunosuppressive agent, 2-chloroadenosine (C1-Ade) or cyclosporin (cys-A) diminished its activity, thereby substantiating an immunomodulatory mechanism. Noni-ppt was also capable of stimulating the release of several mediators from murine effector cells, including tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-10, IL-12 p70, interferon-gamma (IFN-gamma) and nitric oxide (NO), but had no effect on IL-2 and suppressed IL-4 release. Improved survival time and curative effects occurred when noni-ppt was combined with sub-optimal doses of the standard chemotherapeutic agents, adriamycin (Adria), cisplatin (CDDP), 5-fluorouracil (5-FU), and vincristine (VCR), suggesting important clinical applications of noni-ppt as a supplemental agent in cancer treatment.

Antileukemic activity of Viva-Natural, a dietary seaweed extract, on Rauscher murine leukemia in comparison with anti-HIV agents, azidothymidine, dextran sulfate and pentosan polysulfate.

An antileukemic activity of partially purified polysaccharide of an edible seaweed. Viva-Natural, against Rauscher murine retrovirus-induced erythroleukemia has been demonstrated. This antileukemic effect is compared with standard anti-human immunodeficiency virus (HIV) agents, azidothymidine (AZT), dextran sulfate and pentosan polysulfate. Pretreatment with Viva-Natural, as an immunomodulator, on day 3 prior to the virus inoculation demonstrated definite prophylactic activity, while pretreatment with the other three anti-HIV agents showed no prophylactic activity. The replication of Rauscher virus in BALB/3T3 cell cultures accompanied by direct cytopathic effect (syncytia formation) was suppressed in the presence of Viva-Natural or the other anti-HIV agents in the culture medium. In spite of the antiviral potentials of the four agents in vitro, only Viva-Natural and AZT demonstrated therapeutic efficacy against Rauscher leukemia in mice.

Anticancer potential of Viva-Natural, a dietary seaweed extract, on Lewis lung carcinoma in comparison with chemical immunomodulators and on cyclosporine-accelerated AKR leukemia.

Viva-Natural, extracted from a dietary seaweed, containing a macrophage-activating polysaccharide, has been confirmed to be active against intraperitoneally implanted Lewis lung carcinoma (LLC) and spontaneous AKR T cell leukemia. The antitumor potential against LLC has been evaluated in comparison with standard synthetic immunomodulators such as pyran copolymer (MVE-2), isoprinosine, levamisole, and tilorone while manipulating the immune systems by immunosuppressive agents, cyclophosphamide (CY) and 2-chloroadenosine. The anti-LLC activity of Viva-Natural has been found to be superior to that of isoprinosine but inferior to that of MVE-2. LLC-enhancing effect of CY could be partially reserved by the subsequent administration of Viva-Natural or MVE-2 but not by isoprinosine. 2-Chloroadenosine, a specific macrophage inhibitor, abrogated the anti-LLC activity of Viva-Natural and isoprinosine but not the activity of MVE-2. Levamisole and tilorone showed no anti-LLC activity. Ethanol-precipitable fraction of water-soluble part of Viva-Natural (crude polysaccharide) demonstrated curative activity similar to that of MVE-2. Viva-Natural reversed the potentiation effect of ciclosporin on the development of leukemia in AKR mice at preleukemic stage.

Effect of pretazettine and viva-natural, a dietary seaweed extract, on spontaneous AKR leukemia in comparison with standard drugs.

Antileukemic activity of pretazettine hydrochloride (PTZ: a narcissus alkaloid) and Viva-Natural (a seaweed extract) has been confirmed against spontaneous AKR T cell leukemia in mice containing 20% of advanced leukemia. The activity of both agents has been compared with selected standard cytotoxic drugs, vincristine (VCR), methotrexate (MTX), 6-thioguanine (6-TG), and adriamycin (ADR), and immunomodulators, pyran copolymer (MVE-2), isoprinosine, levamisole and tilorone. PTZ activity seems to be superior (90% increase in life span, ILS) to those of MTX (71% ILS), 6-TG (60%), and ADR (49%), and inferior to VCR (114% ILS). Viva-Natural has been found to be the only immunomodulator (61%) active against AKR T cell leukemia, while all standard immunomodulators tested were not active. Combination treatment of PTZ with VCR, or 6-TG, or ADR, or Viva-Natural were synergistic, but combination of PTZ with MTX was not beneficial. PTZ or VCR has been found to be therapeutically very effective (323 or 347% ILS, respectively) against mice in advanced stage of leukemia, and induced complete clinical remissions. Also, PTZ has been found to reverse the leukemia-enhancing effect of ciclosporin in AKR mice at preleukemic stage.

Anticancer activity of a natural product, viva-natural, extracted from Undaria pinnantifida on intraperitoneally implanted Lewis lung carcinoma.

A natural product, named Viva-Natural, extracted from a dietary seaweed Undaria pinnantifida has been found to be therapeutically active against Lewis lung carcinoma (LLC). Viva-Natural also demonstrated moderate prophylactic activity against LLC in allogeneic mice. The active principle(s) which was concentrated in the water-insoluble fraction of Viva-Natural was essentially noncytotoxic in KB cell cultures, and probably a polysaccharide. Viva-Natural was found to be significantly effective in enhancing the natural cytolytic activity of peritoneal macrophages against KB cells as targets in in vitro assay, suggesting that the antitumor action of Viva-Natural might be indirect through the activation of nonspecific immune systems. A combination therapy of Viva-Natural and standard anticancer drugs was additively or synergistically effective.

Therapeutic activity of pretazettine, a narcissus alkaloid, on spontaneous AKR leukemia.

A narcissus alkaloid, pretazettine hydrochloride (PTZ) has been shown to be active against spontaneous AKR leukemia. The long-term treatment with PTZ begining at 5--7 months of age of a group of AKR mice containing 10--20% of advanced leukemic mice significantly prolonged the life span of the group. The therapeutic effectiveness of PTZ has been compared with several standard antileukemic drugs. PTZ decreased the AKR virus titer in the circulating blood of mice and its antiviral activity in AKR virus infected NIH/3T3 cells has been confirmed by XC assay.

Therapeutic activity of pretazettine on Rauscher leukemia: combination of antiviral activity and cellular protein inhibition.

Pretazettine hydrochloride (PTZ) has been found to inhibit protein synthesis, without being inhibitory to DNA and RNA, in Rauscher leukemic blood cells in mice for at least 6 h after its administration. With comparison to Virazole and cycloheximide, the specific anti-Rauscher virus activity of PTZ has been demonstrated only in acutely-infected NIH/3T3 cells but not in chronically-infected cells. It is not certain that the inhibitory action of PTZ on reverse transcriptase is contributory to its therapeutic activity in leukemic mice.

Therapeutic activity of pretazettine, a narcissus alkaloid on Rauscher leukemia: comparison with tazettine and streptonigrin.

The therapeutic activity of narcissus alkaloid pretazettine HC1 (PTZ) on established Rauscher leukemia has been demonstrated and compared with the isomer tazettine (TZ) and an antibiotic, streptonigrin (SN). PTZ and SN showed remarkable prolongation effect on the life span of the leukemic mice and the antiviral activity has been confirmed in mouse 3T3 cells infected with Rauscher virus. TZ showed no significant activity in the leukemic mice and was inhibitory to the virus growth in the cells at much higher doses than PTZ. It is suggested that the stereochemical rearrangement from PTZ to TZ inactivates the biological activity of PTZ.

Combination chemotherapy of Rauscher leukemia and ascites tumors by narcissus alkaloid with standard drugs and effect on cellular immunity.

The therapeutic activity of the narcissus residual alkaloid A-2 against Rauscher leukemia has been compared with 10 standard anticancer drugs, and synergistic or additive combination pairs have been selected using a viral leukemia and two transplantable tumor systems. An increased beneficial effect has been demonstrated by a combination of the alkylating and DNA-binding agents and the alkaloid against the three malignant tumors, while a beneficial effect by combining the alkaloid and the antimetabolites (either 6-MP or 5-azacytidine) was seen only against the viral leukemia. The alkaloid has no suppressive activity against cellular immunity as tested by PHA reactivity and allogeneic tumor rejection systems.