The use of lentinan for treating gastric cancer

Abstract

Natural compounds containing fungal β-glucans have been used to improve general health for thousands of years in China and Japan. Lentinan, the backbone of β-(1, 3)-glucan with β-(1, 6) branches, is one of the active ingredients purified from Shiitake mushrooms and has been approved as a biological response modifier for the treatment of gastric cancer in Japan. Despite recent advances in chemotherapeutic agents, unresectable or recurrent gastric cancer remains an incurable disease, with survival rates being far from satisfactory. Recent clinical studies have shown that chemo-immunotherapy using lentinan prolongs the survival of patients with advanced gastric cancer, as compared to chemotherapy alone. In addition, trastuzumab, an antibody against HER2/neu growth factor receptor, has been used for the treatment of gastric cancer in combination with cytotoxic chemotherapeutic agents. Lentinan may exert a synergistic action with anti-cancer monoclonal antibodies to activate complement systems through the mechanism of antibody-dependent cellular cytotoxicity and complement dependent cytotoxicity. Because a better understanding of its biological activities should enable us to use lentinan more efficiently in the treatment of gastric cancer, immunological effects provided by β-glucans, a possible mode of action of lentinan, and its clinical application including future potential uses are discussed in the present review.

Fig. (1)

The structure of β-glucans [34]. β-glucans from fungi consist of a backbone of β-(1, 3)-glucan with various degrees of β-(1, 6) glucan branching.

Fig. (2)

Examples of structures of microbial β-glucans showing the branching patterns of their repeating units [6].

Fig. (3)

Possible fungal β-glucan mediated signal pathways [6].

Fig. (4)

The structure of lentinan.

Fig. (5)

Comparison of the granulocyte/lymphocyte ratio between patients who received (Lentinan+) and those who did not (Lentinan-) using the x² test [73]. A: Before therapy. B: At either 1 year after initiation of the S-1 based chemotherapy or 1 mo prior to death (cases in which the survival time was < 1 year after starting chemotherapy). P values of less than 0.05 were considered statistically significant. G/L ratio: Granulocyte/lymphocyte ratio.

Fig. (6)

Kaplan-Meier curves of overall survival [73]. Lentinan+: The group that received chemo-immunotherapy with lentinan. Lentinan-: The group that received S-1 based chemotherapy alone. OS: overall survival.

Fig. (7)

Synergy of β-glucan with anti-HER2 antibody (Herceptin) against human breast carcinoma BT474 xenografts in nude mice [64]. In contrast to controls (solid circles), Herceptin (open squares), or β-glucan controls (BG: solid squares), the combination of Herceptin and β-glucan (open circles) significantly suppressed tumor growth (P = 0.002).