Honokiol: A potent chemotherapy candidate for human colorectal carcinoma

Abstract

AIM:To investigate the anticancer activity of Honokiol on RKO, a human colorectal carcinoma cell line in vitro and in vivo, and to evaluate its possible use in clinic. METHODS:In vitro anticancer activity of honokiol was demonstrated by its induction of apoptosis in tumor cells. We analyzed cell proliferation with MTT assay, cell cycle with flow cytosmeter, DNA fragment with electrophoresis on agarose gels. To test the mechanism of honokiol-induced apoptosis, Western blotting was used to investigate the factors involved in this process. The pharmacokinetics study of honokiol was tested by high phase liquid chromatography. In in vivo study, Balb/c nude mice were incubated with RKO cells. Honokiol was injected intraperitoneally every other day into tumor bearing Balb/c nude mice. RESULTS:Our results showed that honokiol induced apoptosis of RKO cells in a time-and dose-dependent manner. At 5-10 ug/mL for 48 h, honokiol induced apoptosis through activating Caspase cascades. Pharmacokinetics study demonstrated that, honokiol could be absorbed quickly by intraperitoneal injection, and maintained in plasma for more than 10 h. In nude mice bearing RKO-incubated tumor, honokiol displayed anticancer activity by inhibiting tumor growth and prolonging the lifespan of tumor bearing mice. CONCLUSION:With its few toxicity to normal cells and potent anticancer activity in vitro and in vivo, honokiol might be a potential chemotherapy candidate in treating human colorectal carcinoma.Chen F, Wang T, Wu YF, Gu Y, Xu XL, Zheng S, Hu X. Honokiol: A potent chemotherapy candidate for human colorectal carcinoma.

Honokiol, a natural biphenyl, inhibits in vitro and in vivo growth of breast cancer through induction of apoptosis and cell cycle arrest

“…Growth inhibition was observed in all breast cancer cell lines tested, regardless of their HR, HER2 or p53 status, but it was not observed for glioblastoma multiforme cells. Similar to other tumors (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), our studies revealed LC50 at a range of 29-50 μM for breast cancer cell lines. Of interest, the lowest LC50 values were observed for the HR-negative, p53-mutated MDA-MB-231 and SK-BR-3 cell lines.…”

“…administration, its serum half-life is >5 h, and its plasma concentration is similar to the concentration needed to induce in vitro cytotoxicity against breast cancer (36)(37)(38)(39). Moreover, HNK administration was well tolerated and no weight loss or other major side effects were observed in this and in previous other animal studies (13,19,37). Thus, HNK administration, at effective doses to treat breast cancer, seems to be safe and feasible.…”

“…Moreover, chemotherapy is currently the only therapeutic option for HR-negative, HER2-negative (triple negative) breast tumors (27). Importantly, the doses of HNK in this study do not affect the growth of normal mononuclear cells, fibroblasts, lymphocytes (11,13,19) or glioblastoma cells (present study). Thus, HNK effect seems to be cell-and tumor-type specific.…”

“…We and others observed in vivo activity of HNK against angiosarcomas (19), colon (13) and breast cancers (present study) following i.p. administration of 100-120 mg/kg.…”

“…In the promyelocytic cell line HL-60, HNK induces differentiation, and shows cytostatic activity (7)(8)(9), and in B-cell chronic lymphocytic leukemia (B-CLL) and multiple myeloma, it induces caspase-dependent and -independent apoptosis, enhances cell kill and overcomes resistance to cytotoxic chemotherapy (10)(11)(12). HNK was also shown to have potent cytotoxic activities against colon and lung cancers, hepatoma and skin tumors (13)(14)(15)(16)(17). Interestingly, HNK has also been shown recently to overcome the multidrug resistance (MDR) of the breast cancer cell line MCF-7/ ADR (18).…”